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Diss Factsheets

Administrative data

Description of key information

HATCOL 5236:

Acute Oral Toxicity: LD50 >2000 mg/kg bw in male & female Wistar rats.

Acute Dermal Toxicity: LD50 >2000 mg/kg bw in male & female Wistar rats.

HATCOL 3344:

Acute Oral Toxicity: LD50 >2000 mg/kg bw in male & female Wistar rats.

Acute Dermal Toxicity: LD50 >2000 mg/kg bw in male & female Wistar rats.

HATCOL 3331:

Acute Oral Toxicity: LD50 >2000 mg/kg bodyweight in male and female Wistar rats.

Acute Dermal Toxicity: LD50 >2000 mg/kg bodyweight in male and female Wistar rats.

Reaction product of pentaerythritol and trimethylolpropane with n-pentanoic acid, 2-methylbutyric acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid and n-decanoic acid

Acute Oral Toxicity: LD50 > 5000 mg/kg bodyweight in male and female rats

Acute Dermal Toxicity: LD50 > 2000 mg/kg bodyweight in male and female rats

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 November 2002 to 12 December 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD, EU & US EPA testing guidelines in compliance with GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species: Rat, Wistar strain Cri:(Wl) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC). Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 6 Animals. Each dose group consisted of 3 animals of one sex (females were nullparous and non-pregnant).
Age and body weight: Young adult animals (approx. 9 weeks old) were selected. Bodyweight variation did not exceed +1- 20% of the sex mean.
Identification: Earmark.
Conditions: A controlled environment was maintained in the room with optimal conditions considered as being approximately 15 air changes per hour, a temperature of 21±3°C, a relative humidity of 30-70% and 12 hours artificial fluorescent light and 12 hours dark per day. Deviations from the maximum level for relative humidity (with a maximum of 20%) occurred which might have been caused by cleaning procedures in the room. Based on laboratory historical data these deviations were considered not to have affected the study integrity.
Accommodation: Group housing of 3 animals per sex per cage in labelled Macrolon cages (type IV; height 18 cm.) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany). Certificates of analysis were examined and then retained in the NOTOX archives. Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Free access to standard pelleted laboratory animal diet (from A1tromin (code VRF 1), Lage, Germany). Certificates of analysis were examined and then retained in the NOTOX archives.
Water: Free access to tap-water. Certificates of quarterly analysis were examined and then retained in the NOTOX archives.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test substance was dosed undiluted as delivered by the sponsor.
The toxicity of the test substance was assessed by stepwise treatment of groups of 3 animals.
Doses:
The first group was treated at a dose level of 2000 mg/kg body weight. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.
No. of animals per sex per dose:
6 Animals. Each dose group consisted of 3 animals of one sex.
Control animals:
no
Details on study design:
A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health.
Method: Oral gavage, using a stainless steel stomach tube.
Fasting: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until approximately 3-4 hours after administration of the test substance.
Frequency: Single dosage, on day 1.
Dose level (volume): 2000 mg/g (2.0 ml/kg) body weight. Dose volume calculated as dose level: specific gravity.

Observations
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration). 8 and 15
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy: At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
other: Hunched posture was noted in all animals on day 1.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
No further findings detailed in the study report.

TABLE 1: CLINICAL SIGNS

TEST DAY

 

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

HOURS AFTER TREATMENT

MAX GRADE

0

2

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

FEMALES 2000 MG/KG

ANIMAL 1

POSTURE

-HUNCHED POSTURE

(1)

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 2

POSTURE

-HUNCHED POSTURE

(1)

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 3

POSTURE

-HUNCHED POSTURE

(1)

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

MALES 2000 MG/KG

ANIMAL 4

POSTURE

-HUNCHED POSTURE

(1)

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 5

POSTURE

-HUNCHED POSTURE

(1)

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 6

POSTURE

-HUNCHED POSTURE

(1)

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

 

TABLE 2: BODYWEIGHTS (GRAM)

SEX/DOSE LEVEL

ANIMAL

DAY 1

DAY 8

DAY 15

FEMALES 2000 MG/KG

 

1

193

234

251

 

2

183

228

247

 

3

198

244

260

 

MEAN

191

235

253

 

ST.DEV.

8

8

7

 

N

3

3

3

MALE 2000 MG/KG

 

4

319

413

464

 

5

313

383

420

 

6

309

379

423

 

MEAN

314

392

436

 

ST.DEV.

5

19

25

 

N

3

3

3

 

TABLE 3: MACROSCOPIC FINDINGS

ANIMAL ORGAN

FINDING

DAY OF DEATH

FEMALES 2000 MG/KG

1

No findings noted

Scheduled necropsy Day 15 after treatment

2

No findings noted

Scheduled necropsy Day 15 after treatment

3

No findings noted

Scheduled necropsy Day 15 after treatment

MALES 2000 MG/KG

4

No findings noted

Scheduled necropsy Day 15 after treatment

5

No findings noted

Scheduled necropsy Day 15 after treatment

6

No findings noted

Scheduled necropsy Day 15 after treatment

 

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 value of HATCOL 5236 in Wistar rats was established to exceed 2000 mg/kg bodyweight.
Executive summary:

Assessment of acute oral toxicity with HATCOL 5236 in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in: Environmental Protection Agency (EPA): Health Effects Test Guidelines OPPTS 870.1100. "Acute Oral Toxicity", June 1996; EC Commission Directive 96/54/EC, Part B.1 tris "Acute Toxicity-Oral, Acute Toxic Class Method" and OECD No.423, "Acute Oral Toxicity - Acute Toxic Class Method".

HATCOL 5236 was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg bodyweight. Animals were subjected to daily observations and weekly determination of bodyweight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred.

Hunched posture was noted in all animals on day 1.

The body weight gain shown by the animals over the study period was considered to be normal.

No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50value of HATCOL 5236 in Wistar rats was established to exceed 2000 mg/kgbodyweight.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548IEEC), HATCOL 5236 does not have to be classified and has no obligatory labelling requirement for oral toxicity.

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
4 substances available for read across
Adequacy of study:
weight of evidence
Justification for type of information:
see the attached justification in section 13 for the full details.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Hatcol 5236
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Hatcol 3331
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Hatcol 3344
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Reaction product of pentaerythritol and trimethylolpropane with n-pentanoic acid, 2-methylbutyric acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid and n-decanoic acid
Interpretation of results:
GHS criteria not met
Conclusions:
The read across for substance, CAS: 156558-98-4; EC: 451-190-0; is based upon the analogous substances to which basic form, degree of substitution of functional groups is not considered to effect the proposed read across for the endpoint of acute oral toxicity. The LD50  for the substance based on the mean of the information available is deemed to be 2750 mg/kg bw.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 June 2003 to 10 July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD, EU & US EPAa testing guidelines in compliance with GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species: Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC). Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 6 Animals. Each dose group consisted of 3 animals of one sex (females were nulliparous and non-pregnant).
Age and bodyweight: Young adult animals (approx. 8 weeks old) were selected. Bodyweight variation did not exceed +1- 20% of the sex mean.
Identification: Earmark.
Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0°C (actual range: 17.2 -23.2°C), a relative humidity of 30-70% (actual range: 48 - 83%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
Accommodation: Group housing of 3 animals per sex per cage in labelled Macrolon cages (type IV; height 18 cm.) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany). Certificates of analysis were examined and then retained in the NOTOX archives. Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany). Certificates of analysis were examined and then retained in the NOTOX archives.
Water: Free access to tap-water. Certificates of quarterly analysis were examined and then retained in the NOTOX archives.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test substance was dosed undiluted as delivered by the sponsor.
Doses:
Dose level (volume): 2000 mg/kg (2.062 ml/kg) bodyweight
No. of animals per sex per dose:
6 animals. 3 males & 3 females.
Control animals:
no
Details on study design:
A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health.
Method: Oral gavage, using a stainless steel stomach tube.
Fasting: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance.
Frequency: Single dosage, on day 1.
Dose level (volume): 2000 mg/kg (2.062 ml/kg) bodyweight. Dose volume calculated as dose level: specific gravity.
Mortality/Viability: Twice daily.
Bodyweights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy: At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
No statistical analysis was performed.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortaliy occurred.
Clinical signs:
other: Hunched posiure and piloerection were observed among all females on day 1. Males were without clinical signs.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
No further findings detailed in the study report.

TABLE 1: CLINICAL SIGNS

TEST DAY

MAX GRADE

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

HOURS AFTER TREATMENT

0

2

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

FEMALES 2000 MG/KG

ANIMAL 1

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-HUNCHED POSTURE

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-PILOERCETION

(1)

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 2

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-HUNCHED POSTURE

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-PILOERECTION

(1)

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 3

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-HUNCHED POSTURE

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMGAE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-PILOERECTION

(1)

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

MALES 2000 MG/KG

ANIMAL 4

NO CLINICAL SIGNS NOTED

 

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 5

NO CLINICAL SIGNS NOTED

 

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 6

NO CLINICAL SIGNS NOTED

 

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

- = SIGN NOT OBSERVED / . = OBSERVATION NOT PERFORMED / + = ANIMAL DEAD

 

TABLE 2: BODYWEIGHTS (GRAM)

SEX/DOSE LEVEL

ANIMAL

DAY 1

DAY 8

DAY 15

FEMALES 2000 MG/KG

 

1

167

215

232

 

2

173

216

247

 

3

171

217

237

 

MEAN

170

216

239

 

ST.DEV.

3

1

8

 

N

3

3

3

MALES 2000 MG/KG

 

4

254

321

246

 

5

254

338

381

 

6

263

340

375

 

MEAN

257

333

367

 

ST.DEV.

5

10

19

 

N

3

3

3

 

TABLE 3: MACROSCOPIC FINDINGS

ANIMAL ORGAN

FINDING

DAY OF DEATH

FEMALES 2000 MG/KG

1

No findings noted

Scheduled necropsy Day 15 after treatment

2

No findings noted

Scheduled necropsy Day 15 after treatment

3

No findings noted

Scheduled necropsy Day 15 after treatment

MALES 2000 MG/KG

4

No findings noted

Scheduled necropsy Day 15 after treatment

5

No findings noted

Scheduled necropsy Day 15 after treatment

6

No findings noted

Scheduled necropsy Day 15 after treatment

 

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 value of HATCOL 3331 in Wistar rats was established to exceed 2000 mg/kg bodyweight.
Executive summary:

Assessment of acute oral toxicity with HATCOL 3331 in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in: Environmental Protection Agency (EPA): Health Effects Test Guidelines OPPTS 870.1100. "Acute Oral Toxicity"; EC Commission Directive 96/54/EC, Part B.1 tris "Acute Toxicity-Oral, Acute Toxic Class Method", OECD No.423, "Acute Oral Toxicity - Acute Toxic Class Method" and JMAFF Japanese test guidelines.

HATCOL 3331 was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg bodyweight. Animals were subjected to daily observations and weekly determination of bodyweight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred.

Hunched posture and piloerection were observed among all females on day 1. Males were without clinical signs.

The body weight gain shown by the animals over the study period was considered to be normal.

No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of HATCOL 3331 in Wistar rats was established to exceed 2000 mg/kgbodyweight.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 3331 does not have to be classified and has no obligatory labelling requirement for oral toxicity.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 June 2003 to 10 July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD, EU & US EPA testing guidelines in compliance with GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species: Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC). Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 6 Animals. Each dose group consisted of 3 animals of one sex (females were nullparous and non-pregnant).
Age and body weight: Young adult animals (approx. 8 weeks old) were selected. Bodyweight variation did not exceed +/- 20% of the sex mean.
Identification: Earmark.
Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0°C (actual range: 17.2-23.2°C), a relative humidity of 30-70% (actual range: 48 - 83%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
Accommodation: Group housing of 3 animals per sex per cage in labelled Macrolon cages (type IV; height 18 cm) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany). Certificates of analysis were examined and then retained in the NOTOX archives. Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany). Certificates of analysis were examined and then retained in the NOTOX archives.
Water: Free access to tap-water. Certificates of quarterly analysis were examined and then retained in the NOTOX archives.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test substance was dosed undiluted as delivered by the sponsor.
The objective of this study was to assess the toxicity of the test substance when administered in a single dose to rats of both sexes at one or more defined dosages. Furthermore, the results of the study allowed the test substance to be ranked according to most classification systems, currently in use.
This study should provide a rational basis for risk assessment in man.
The oral route was selected as it is a possible route of human exposure during manufacture, handling or use of the test substance.
The toxicity of the test substance was assessed by stepwise treatment of groups of 3 animals.
The first group was treated at a dose level of 2000 mg/kg body weight. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.
Doses:
2000 mg/kg (2.02 ml/kg) bodyweight.
No. of animals per sex per dose:
3 males and 3 females
Control animals:
no
Details on study design:
TREATMENT
A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health.
Method: Oral gavage, using a stainless steel stomach tube.
Fasting: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance.
Frequency: Single dosage, on day 1.
Dose level (volume): 2000 mg/kg (2.02 ml/kg) body weight. Dose volume calculated as dose level: specific gravity.

OBSERVATIONS
Mortality/Viability: Twice daily.
Bodyweights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy: At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
No statistical analysis was performed.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
other: Hunched posture and piloerection were shown by all males on day 1 and by all females between days 1 and 3. In additon, all males showed lethargy on day 1.
Gross pathology:
No abnormalites were found at macroscopic post mortem examination of the animals.
Other findings:
No futher findings detailed in the study report.

TABLE 1: CLINICAL SIGNS

TEST DAY

MAX GRADE

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

HOURS AFTER TREATMENT

0

2

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

FEMALES 2000 MG/KG

ANIMAL 1

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-HUNCHED POSTURE

(1)

1

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-PILOERECTION

(1)

1

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 2

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-HUNCHED POSTURE

(1)

1

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-PILOERECTION

(1)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 3

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-HUNCHED POSTURE

(1)

1

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-PILOERECTION

(1)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

MALES 2000 MG/KG

ANIMAL 4

BEHAVIOUR

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-LETHARGY

(3)

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-HUNCHED POSTURE

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-PILOERECTION

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 5

BEHAVIOUR

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-LETHARGY

(3)

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-HUNCHED POSTURE

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-PILOERECTION

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 6

BEHAVIOUR

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-LETHARGY

(3)

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

POSTURE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-HUNCHED POSTURE

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-PILOERECTION

(1)

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

- = SIGN NOT OBSERVED/ . = OBSERVATION NOT PERFORMED/ + = ANIMAL DEAD

 

TABLE 2: BODYWEIGHTS (GRAM)

SEX/DOSE LEVEL

ANIMAL

DAY 1

DAY 8

DAY 15

FEMALES 2000 MG/KG

 

1

162

213

225

2

163

210

227

3

162

210

222

MEAN

162

211

225

ST.DEV.

1

2

3

N

3

3

3

MALES 2000 MG/KG

 

4

246

306

344

5

258

320

350

6

259

329

380

MEAN

254

318

358

ST.DEV.

7

12

19

N

3

3

3

 

TABLE 3: MACROSCOPIC FINDINGS

ANIMAL ORGAN

FINDING

DAY OF DEATH

FEMALES 2000 MG/KG

1

No findings noted

Scheduled necropsy Day 15 after treatment

2

No findings noted

Scheduled necropsy Day 15 after treatment

3

No findings noted

Scheduled necropsy Day 15 after treatment

MALES 2000 MG/KG

4

No findings noted

Scheduled necropsy Day 15 after treatment

5

No findings noted

Scheduled necropsy Day 15 after treatment

6

No findings noted

Scheduled necropsy Day 15 after treatment

 

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 value of HATCOL 3344 in Wistar rats was established to exceed 2000 mg/kg bodyweight.
Executive summary:

Assessment of acute oral toxicity with HATCOL 3344 in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in: Environmental Protection Agency (EPA): Health Effects Test Guidelines OPPTS 870.1100. -Acute Oral Toxicity; EC Commission Directive 96/54/EC, Part B.1 tris "Acute Toxicity-oral, Acute Toxic Class Method", OECD No.423, "Acute Oral Toxicity - Acute Toxic Class Method" and JMAFF Japanese test guidelines.

HATCOL 3344 was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kgbodyweight. Animals were subjected to daily observations and weekly determination of bodyweight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred.

Hunched posture and piloerection were shown by all males on day 1 and by all females between days 1 and 3. In addition, all males showed lethargy on day 1.

The body weight gain shown by the animals over the study period was considered to be normal.

No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of HATCOl 3344 in Wistar rats was established to exceed 2000 mg/kgbodyweight.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 334 does not have to be classified and has no obligatory labelling requirement for oral toxicity.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 Jan - 17 Feb 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance Reaction product of pentaerythritol and trimethylolpropane with n-pentanoic acid, 2-methylbutyric acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid and n-decanoic acid. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (ECHA, 2012)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted in 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
The department of health of the government of the United Kingdom
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Sprague-Dawley CD (Crl : CD ® BR)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Margate, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 210-225 g (males); 201-218 g (females)
- Fasting period before study: overnight fasting immediately before dosing and for approximately three to four hours after dosing
- Housing: in groups of up to five by sex in solid–floor polypropylene cages furnished with woodflakes
- Diet: Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham, UK, ad libitum
- Water: mains water, ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 50-67
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5.22 mL/kg bw
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
other: no, not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed for deaths or overt signs of toxicity 1/2, 1, 2, and 4 h after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, and gross pathology
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period
Clinical signs:
other: No clinical signs of toxicity were observed up to the end of the 14-day observation period.
Gross pathology:
Necropsy revealed no substance-related findings
Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
DSD: not classifed
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Klimisch 1-2

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 September 2003 to 15 October 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD, EU, US EPA and Japanese testing guidelines in compliance with GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
other: Japanese Ministr of Agriculture, Forestr and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species: Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC). Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 5 males and 5 females (females were nullparous and nonpregnant).
Age and body weight: Young adult animals (approx. 9 weeks old) were selected. Bodyweight variation did not exceed +/- 20% of the sex mean.
Identification: Earmark
Conditions: Animals were housed in a controlled environment. in which optimal conditions were considered to be approximately 15 air changes per hour. a temperature of 21.0 ± 3.0°C (actual range: 17.2 - 22.3°C), a relative humidity of 30-70% (actual range: 39 -78%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
Accommodation: Individually housed in labelled Macrolon cages (type II, height 15 cm.) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany). Certificates of analysis were examined and then retained in the NOTOX archives. Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany). Certificates of analysis were examined and then retained in the NOTOX archives.
Water: Free access to tap-water. Certificates of quarterly analysis were examined and then retained in the NOTOX archives.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Clipping: One day before exposure (day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
Application: The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm2 for males and 18 cm2 for females. The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminium foil and Coban flexible bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.
Frequency: Single dosage, on day 1.
Application period: 24 hours, after which dressings were removed and the skin cleaned of residual test substance using Water.
Duration of exposure:
24 hours
Doses:
Dose level (volume): 2000 mg/kg (2.0 ml/kg) body weight. Dose volume calculated as follows: dose level: specific gravity.
No. of animals per sex per dose:
5 males and 5 females in the dosing group (2000 mg/kg)
Control animals:
no
Details on study design:
OBSERVATIONS
Mortality/Viability: Twice daily.
Bodyweights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy: At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
Not specified in the study report.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
other: Chromodacryorrhoea (nose), hunched posture and lethargy were noted among the animals. The animals had recovered from the symptoms by day 3. Erythema was were seen in the treated skin-area of one animal on day 3.
Gross pathology:
No abnormaliies were found at macroscopic post mortem examination of the animals.
Other findings:
No further findings detailed in the study report.

TABLE 1: CLINICAL SIGNS

TEST DAY

 

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

HOURS AFTER TREATMENT

MAX GRADE

0

2

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

MALE 2000 MG/KG

ANIMAL 1

SECRETION/EXCRETION

-CHROMODACRYORRHOEA (NOSE)

(3)

-

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 2

SECRETION/EXCRETION

-CHROMODACRYORRHOEA (NOSE)

(3)

-

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 3

SECRETION/EXCRETION

-CHROMODACRYORRHOEA (NOSE)

(3)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 4

POSTURE

-HUNCHED POSTURE

(1)

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

SECRETION/EXCRETION

-CHROMODACRYORRHOEA (NOSE)

(3)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 5

SECTRETION/EXCRETION

-CHROMODACRYORRHOEA (NOSE)

(3)

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

FEMALES 2000 MG/KG

ANIMAL 6

BEHAVIOR

-LETHARGY

(3)

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

SECRETION/EXCRETION

-CHROMODACRYORRHOEA (NOSE)

(3)

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 7

SECRETION/EXCRETION

-CHROMODACRYORRHOEA (NOSE)

(3)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 8

NO CLINICAL SIGNS NOTED

 

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 9

SKIN/FUR/PLUMAGE

-ERYTHEMA MACULATE (TREATED SKIN)

(4)

-

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

SECRETION/EXCRETION

-CHROMODACRYORRHOEA (NOSE)

(3)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 10

SECRETION/EXCRETION

-CHROMODACRYORRHOEA (NOSE)

(3)

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

 

TABLE 2: BODYWEIGHTS (GRAM)

SEX/DOSE LEVEL

ANIMAL

DAY 1

DAY 8

DAY 15

MALES 2000 MG/KG

 

1

373

377

423

 

2

329

346

371

 

3

315

334

356

 

4

334

354

385

 

5

347

369

386

 

MEAN

340

356

384

 

ST.DEV.

22

17

25

 

N

5

54

5

FEMALES 2000 MG/KG

 

6

194

203

217

 

7

240

250

263

 

8

250

254

282

 

9

248

251

273

 

10

200

215

223

 

MEAN

226

235

252

 

ST.DEV.

27

24

30

 

N

5

5

5

 

TABLE 3: MACROSCOPIC FINDINGS

ANIMAL ORGAN

FINDING

DAY OF DEATH

MALES 2000 MG/KG

1

No findings noted

Scheduled necropsy Day 15 after treatment

2

No findings noted

Scheduled necropsy Day 15 after treatment

3

No findings noted

Scheduled necropsy Day 15 after treatment

4

No findings noted

Scheduled necropsy Day 15 after treatment

5

No findings noted

Scheduled necropsy Day 15 after treatment

FEMALES 2000 MG/KG

6

No findings noted

Scheduled necropsy Day 15 after treatment

7

No findings noted

Scheduled necropsy Day 15 after treatment

8

No findings noted

Scheduled necropsy Day 15 after treatment

9

No findings noted

Scheduled necropsy Day 15 after treatment

10

No findings noted

Scheduled necropsy Day 15 after treatment

 

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of HATCOL 5236 in Wistar rats was established to exceed 2000 mg/kg bodyweight.
Executive summary:

Assessment of acute dermal toxicity with HATCOL 5236 in the rat.

The study was carried out based on the guidelines described in: "Acute Toxicity-Dermal", OECD No.402 (1987); "Acute Dermal Toxicity, EC Commission Directive 921691EEC, Part B.3 (1992); Environmental Protection Agency (EPA): Health Effects Test Guidelines OPPTS 870.1200 (1996), "Acute Dermal Toxicity" and JMAFF: Japanese Test Guidelines (2000).

HATCOL 5236 was administered to five Wistar rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred.

Chromodacryorrhoea (nose), hunched posture and lethargy were noted among the animals. The animals had recovered from the symptoms by day 3. Eryhema was were seen in the treated skin-area of one animal on day 3.

The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.

No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of HA TCOL 5236 in Wistar rats was established to exceed 2000 mg/kgbodyweight.

Based on these results and according to the:

-OECD Harmonized Integrated Hazard Classification System for Human Health and Environmental Effects of Chemical Substances (OECD, 1998), HATCOL 5236 does not have to be classified for acute toxicity by the dermal route.

-EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 5236 does not have to be classified and has no obligatory labelling requirement for dermal toxicity.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 July 2003 to 16 July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD, EU, US EPA and Japanese testing guidelines in compliance with GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent par!ial revisions.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species: Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC) Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 5 males and 5 females (females were nulliparous and nonpregnant).
Age and bodyweight: Young adult animals (approx. 9-10 weeks old) were selected. Bodyweight variation did not exceed +/- 20% of the sex mean.
Identification: Earmark
Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0°C (actual range: 17.2 - 23.7°C), a relative humidity of 30-70% (actual range: 44 - 83%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
Accommodation: Individually housed in labelled Macrolon cages (type III, height 15 cm.) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany). Certificates of analysis were examined and then retained in the NOTOX archives. Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany). Certificates of analysis were examined and then retained in the NOTOX archives.
Water: Free access to tap-water. Certificates of quarterly analysis were examined and then retained in the NOTOX archives.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test substance was dosed undiluted as delivered by the sponsor.

A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.
Method: Dermal application.
Clipping: One day before exposure (day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
Application: The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm for males and 18 cm for females. The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch successively covered with aluminium foil and Coban flexible bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.
Frequency: Single dosage, on day 1.
Dose level (volume): 2000 mg/kg (2.061 ml/kg) body weight. Dose volume calculated as follows: dose level: specific gravity.
Application period: 24 hours, after which dressings were removed and the skin cleaned of residual test substance using water.
Duration of exposure:
24 hours
Doses:
Single does of 2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
Mortality/Viability: Twice daily.
Bodyweights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy: At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
No statistical analysis was performed.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
other: Hunched posture and/or chromodacryorrhoea were noted among all animals on day 2. In addition, maculate erythema or scales were seen on the treated skin site of one male and female between days 3 and 7.
Gross pathology:
No abnormalities were found at macroscopic post mor!em examination of the animals.
Other findings:
No further findings detailed in the study report.
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of HATCOL 3331 in Wistar rats was established to exceed 2000 mg/kg bodyweight.
Executive summary:

Assessment of acute dermal toxicity with HATCOL 3331 in the rat.

The study was carried out based on the guidelines described in: Environmental Protection Agency (EPA): Health Effects Test Guidelines OPPTS 870.1200. "Acute Dermal Toxicity", EC Commission Directive 92/69/EEC, Part B.3, "Acute Toxicity-Dermal", OECD No.402, "Acute Dermal Toxicity" and JMAFF: Japanese Test Guidelines.

HATCOL 3331 was administered to five Wistar rats of each sex by dermal application at 2000 mg/kg bodyweight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred.

Hunched posture and/or chromodacryorrhoea were noted among all animals on day 2. In addition, maculate erythema or scales were seen on the treated skin site of one male andfemale between days 3 and 7.

The bodyweight gain during the observation period was within the range expected for rats used in this type of study.

No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of HATCOL 3331 in Wistar rats was established to exceed 2000 mg/kgbodyweight.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 3331 does not have to be classified and has no obligatory labelling requirement for dermal toxicity.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 July 2003 to 23 July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD, EU, US EPA & Japanese testing guidelines in compliance with GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species: Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC). Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 5 males and 5 females (females were nullparous and non pregnant).
Age and body weight: Young adult animals (approx. 8 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.
Identification: Earmark
Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0°C (actual range: 18.1- 23.7°C), a relative humidity of 30-70% (actual range: 44-78%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
Accommodation: Individually housed In labelled Macrolon cages (type III height 15 cm.) containing purified sawdust as bedding material (SAWI, Jetu Werk. Rosenberg, Germany). Certificates of analysis were examined and then retained in the NOTOX archives. Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Free access to standard pelleted laboratory animal diet (from A1tromin (code VRF i), Lage, Germany). Certificates of analysis were examined and then retained in the NOTOX archives.
Water: Free access to tap-water. Certificates of quarterly analysis were examined and then retained in the NOTOX archives.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
A health Inspection was performed prior to commencement of treatment to ensure that the animals were In a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.
Method: Dermal application.
Clipping: One day before exposure (day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
Application: The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm2 for males and 18 cm2 for females. The test substance was held in contact with the skin with a dressing. consisting of a surgical gauze patch (Surgy 1D) successively covered with aluminium foil and Coban flexible bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.
Dose volume calculated as follows: dose level: specific gravity.
Duration of exposure:
24 hours, after which dressings were removed and the skin cleaned of residual test substance using water.
Doses:
Frequency: Single dosage on day 1.
Dose level (volume): 2000 mg/kg (2.02 ml/kg) body weight.
No. of animals per sex per dose:
5 males & 5 females dosed at 2000 mg/kg/bw.
Control animals:
no
Details on study design:
OBSERVATIONS
Mortality/Viability: Twice daily.
Bodyweights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy: At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
No statistical analysis was performed.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
other: All females and some males showed scales, scabs and/or general/maculate erythema on the treated skin site during the observation period from day 3 onwards. In addition chromodacryorrhoea was noted among some animals on days 1 and/or 2, with diarrhoea in o
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
No further findings detailed in the study report.

TABLE 1: CLINICAL SIGNS

TEST DAY

MAX GRADE

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

HOURS AFTER TREATMENT

0

2

4

 

MALES 2000 MG/KG

ANIMAL 1

NO CLINICAL SIGNS NOTED

 

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 2

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-SCALES (TREATED SKIN)

(3)

-

-

-

-

-

-

-

-

1

1

1

1

1

1

1

1

1

-SCABS (TREATED SKIN)

(3)

-

-

-

-

-

-

-

-

1

1

1

1

1

2

2

1

1

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-CHROMODACRYORRHOEA (NOSE)

(3)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 3

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-DIARRHOEA

(1)

-

-

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-CHROMODACRYORRHOEA (SNOUT)

(3)

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 4

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-CHROMODACRYORRHOEA (NOSE)

(3)

1

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 5

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-GENERAL ERYTHEMA (TREATED SKIN)

(4)

-

-

-

-

1

1

1

-

-

-

-

-

-

-

-

-

-

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

CHROMODACRYORRHOEA (SNOUT)

(3)

-

1

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

FEMALES 2000 MG/KG

ANIMAL 6

SKIN/FUR//PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-ERYTHEMA MACULATE (TREATED SKIN)

(4)

-

-

-

-

2

2

1

1

1

1

1

1

1

1

-

-

-

-SCALES (TREATED SKIN)

(3)

-

-

-

-

-

-

-

-

1

1

1

1

1

1

1

1

1

-SCABS (TREATED SKIN)

(3)

-

-

-

-

-

-

-

1

1

1

1

1

1

1

1

1

1

ANIMAL 7

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-ERYTHEMA MACULATE (TREATED SKIN)

(4)

-

-

-

-

1

1

1

1

1

-

-

-

-

-

-

-

-

-SCALES (TREATED SKIN)

(3)

-

-

-

-

-

-

-

-

1

-

-

-

-

-

-

-

-

-SCABS (TREATED SKIN)

(3)

-

-

-

-

-

-

-

1

1

1

1

1

1

1

1

1

1

SECRETION/EXCRETION

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-CHROMODACRYORRHOEA (SNOUT)

(3)

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ANIMAL 8

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-SCALES (TREATED SKIN)

(3)

-

-

-

-

-

-

-

-

1

1

-

-

-

-

-

-

-

ANIMAL 9

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-SCALES (TREATED SKIN)

(3)

-

-

-

-

-

-

-

-

1

1

-

-

-

-

-

-

-

ANIMAL 10

SKIN/FUR/PLUMAGE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-SCALES (TREATED SKIN)

(3)

-

-

-

-

1

1

1

1

1

1

1

1

1

-

-

-

-

-SCABS (TREATED SKIN)

(3)

-

-

-

-

-

-

-

-

-

-

-

-

-

1

1

1

1

- = SIGN NOT OBSERVED/ . = OBSERVATION NOT PERFORMED/ + = ANIMAL DEAD

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of HATCOL 3344 in Wistar rats was established to exceed 2000 mg/kg bodyweight.
Executive summary:

Assessment of acute dermal toxicity with HATCOL 3344 in the rat.

The study was carried out based on the guidelines described in: Environmental Protection Agency (EPA): Health Effects Test Guidelines OPPTS 870.1200. "Acute Dermal Toxicity, ECCommission Directive 92169/EEC, Part B.3, "Acute Toxicity-Dermal" OECD No 402, "AcuteDermal Toxicity" and JMAFF: Japanese Test Guidelines.

HATCOL 3344 was administered to five Wistar rats of each sex by dermal application at 2000mg/kg body weight for 24 hours. Animals were subjected to daily observations and weeklydetermination of bodyweight. Macroscopic examination was performed after terminal sacrifice(day 15).

No mortality occurred.

All females and some males showed scales, scabs and/or general maculate erythema on the treated skin site during the observation period from day 3 onwards. In addition chromodacryorrhoea was noted among some animals on days 1 and/or 2, with diarrhoea in one male between days 2 and 4.

The bodyweight gain during the observation period was within the range expected for rats used in this type of study.

No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of HATCOL 3344 in Wistar rats was established to exceed 2000 mg/kgbodyweight.

Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), HATCOL 3344 does not have to be classified and has no obligatory labelling requirement for dermal toxicity.

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
4 substances available for read across
Adequacy of study:
weight of evidence
Justification for type of information:
see the attached justification in section 13 for the full details.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Doses:
.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Hatcol 3344
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Hatcol 5236
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Hatcol 3331
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Reaction product of pentaerythritol and trimethylolpropane with n-pentanoic acid, 2-methylbutyric acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid and n-decanoic acid
Interpretation of results:
GHS criteria not met
Conclusions:
The read across for substance, CAS: 156558-98-4; EC: 451-190-0; is based upon the analogous substances to which basic form, degree of substitution of functional groups is not considered to effect the proposed read across for the endpoint of acute dermal toxicity. The LD50  for the substance based on the mean of the information available is deemed to be > 2000 mg/kg bw.
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
3 Feb - 17 Feb 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance Reaction product of pentaerythritol and trimethylolpropane with n-pentanoic acid, 2-methylbutyric acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid and n-decanoic acid. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (ECHA, 2012)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted in 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
The department of health of the government of the United Kingdom
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Sprague-Dawley CD (Crl : CD ® BR)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Margate, UK
- Age at study initiation: 8 – 12 weeks
- Weight at study initiation: 212-227 g (males), 206-216 g (females)
- Housing: the animals were housed individually during 24 h exposure period and in groups of five, by sex, for the remainder of the study in suspended polypropylene cages furnished with woodflakes
- Diet: Rat and Mouse Expanded Diet No.1. Special Diets Services Limited, Witham, UK, ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 47-61
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks of each animal
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: a piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. The bandage was further secured with a piece of Blenderm wrapped around each end.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the residue test material was removed with cotton wool moistened with distilled water
- Time after start of exposure: 24 h
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed for deaths or overt signs of toxicity ½, 1, 2, and 4 hours after dosing and subsequently once daily for fourteen days.
- Necropsy of survivors performed: yes
- Other examinations performed: incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, body weight changes, mortality and any other toxicological effects.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
other: No clinical signs of toxicity were observed up to the 14-day observation period.
Gross pathology:
Necropsy examination revealed no substance-related findings.
Interpretation of results:
GHS criteria not met
Conclusions:
CLP : not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Klimisch 1-2

Additional information

HATCOL 5236:

Acute Oral Toxicity: Assessment of acute oral toxicity with HATCOL 5236 in the rat (Acute Toxic Class Method). HATCOL 5236 was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg bodyweight. Animals were subjected to daily observations and weekly determination of bodyweight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred. Hunched posture was noted in all animals on day 1. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of HATCOL 5236 in Wistar rats was established to exceed 2000 mg/kgbodyweight.

Acute Dermal Toxicity: Assessment of acute dermal toxicity with HATCOL 5236 in the rat. HATCOL 5236 was administered to five Wistar rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred. Chromodacryorrhoea (nose), hunched posture and lethargy were noted among the animals. The animals had recovered from the symptoms by day 3. Eryhema was were seen in the treated skin-area of one animal on day 3. The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity. No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of HATCOL 5236 in Wistar rats was established to exceed 2000 mg/kgbodyweight.

HATCOL 3344:

Acute Oral Toxicity: HATCOL 3344 was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg bodyweight. Animals were subjected to daily observations and weekly determination of bodyweight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred. Hunched posture and piloerection were shown by all males on day 1 and by all females between days 1 and 3. In addition, all males showed lethargy on day 1. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of HATCOL 3344 in Wistar rats was established to exceed 2000 mg/kgbodyweight.

Acute Dermal Toxicity: HATCOL 3344 was administered to five Wistar rats of each sex by dermal application at 2000mg/kg body weight for 24 hours. Animals were subjected to daily observations and weeklydetermination of bodyweight. Macroscopic examination was performed after terminal sacrifice(day 15).

No mortality occurred. All females and some males showed scales, scabs and/or general maculate erythema on the treated skin site during the observation period from day 3 onwards. In addition chromodacryorrhoea was noted among some animals on days 1 and/or 2, with diarrhoea in one male between days 2 and 4. The bodyweight gain during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of HATCOL 3344 in Wistar rats was established to exceed 2000 mg/kg bodyweight.

HATCOL 3331:

Acute Oral Toxicity: HATCOL 3331 was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg bodyweight. Animals were subjected to daily observations and weekly determination of bodyweight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred. Hunched posture and piloerection were observed among all females on day 1. Males were without clinical signs. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of HA TCOL 3331 in Wistar rats was established to exceed 2000 mg/kgbodyweight.

Acute Dermal Toxicity: HATCOL 3331 was administered to five Wistar rats of each sex by dermal application at 2000 mg/kg bodyweight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred. Hunched posture and/or chromodacryorrhoea were noted among all animals on day 2. In addition, maculate erythema or scales were seen on the treated skin site of one male andfemale between days 3 and 7. The bodyweight gain during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of HATCOL 3331 in Wistar rats was established to exceed 2000 mg/kgbodyweight.

PE/TMP tetra/tri C5, i-C5, C7, C8, i-C9, C10 ester

Acute Oral Toxicity: LD50 5000 mg/kg bodyweight in male and female Wistar rats.

For PE/TMP tetra/tri C5, i-C5, C7, C8, i-C9, C10 ester an acute oral toxicity study (limit test) according to OECD TG 401 (Allen, 1998) is available. Groups of 5 male and female Sprague-Dawley rats received doses of 5000 mg/kg bw by gavage. The animals were observed for 14 days. No mortality, signs of systemic toxicity and no abnormalities in body weight gain and during gross necropsy were seen. Thus, the acute oral LD 50 was determined to be greater than 5000 mg/kg bw.

In the acute dermal toxicity study with the PE/TMP tetra/tri C5, i-C5, C7, C8, i-C9, C10 ester no substance-related mortalities were observed after dermal application of the test substance at a limit dose of 2000 mg/kg bw in male and female Sprague-Dawley rat (according to OECD TG 402 and GLP compliance). No clinical signs of toxicity were observed up to the 14-day observation period. Body weight gains of all dose groups were within the normal ranges in males and females during the whole study period. Necropsy examination revealed no substance-related findings. Based on the result of this study, the dermal LD50 value of the test substance for male and female rabbits was greater than 2000 mg/kg bw (Allen, 1998).

Justification for classification or non-classification

The read across for substance, CAS: 156558 -98 -4; EC: 451 -190-0; is based upon the analogous substance to which basic form, degree of substitution of functional groups is not considered to effect the proposed read across for the endpoint of acute toxicity. Based on the available information from the read across substances, the substance subject to registration is not expected to meet the criteria for classifying as acutely toxic via the oral or dermal routes.