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Administrative data

Description of key information

The acute oral LD50 is between 600 and 1650 mg/kg bw. The acute dermal LD50 is > 2000 mg/kg bw. No data are available for acute inhalation toxicity.

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:
weight of evidence
Study period:
1997-09-12 to 1997-09-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague-Dawley, Indianapolis, Indiana
- Age at study initiation: 6 to 10 weeks
- Weight at study initiation: 202 - 220 g
- Fasting period before study: Yes, overnight
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
Temperature, humidity and light controlled room (DHEW publication No. 86-23 (NIH))

IN-LIFE DATES: From: 1997-09-12 To: 1997-09-26
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 33%
- Dosage volume: 1.01 - 1.10 g
Metal dosing cannula
Doses:
5 g/kg bw (1650 mg active/kg bw)
No. of animals per sex per dose:
five males/five females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations - frequently on day of dosing (1, 2.5 and 4 hours) and once daily thereafter; bodyweights on study initiation, at 7 and 14 days post-administration and at death.
- Necropsy of survivors performed: yes
Statistics:
Calculations of the LC50 and 95% confidence limits: Method of moving averages, Weil CC (1952) table for convenient calculations of median effective dose (LD50 and ED50) and instruction in their use. Biometrics, 8.
Preliminary study:
Not performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
< 5 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
< 1 650 mg/kg bw
Based on:
act. ingr.
Mortality:
8/10 rats died by Day 1 of the post-administration period. The remaining two rats (2 x male) dosed with the test material survived until Day 14 of the post-administration period.
Clinical signs:
salivation and hypoactivity were observed by the 2.5 and 4 hour observation periods for the three males that died. There were no clinical signs of toxicty observed in any of the females.
Body weight:
Body weight of the two surviving animals increased up to Day 14.
Gross pathology:
Occurred only in animals that died during the course of the study:
External observations: bloody muzzle and wet tail
Internal observations: confined to the gastrointestinal tract, stomach and small intestine distended with gas and fluid, small intestine appeared red with haemorrhagic sites.
Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral administration of a 33% solution of the test material (5 g/kg bw) resulted in an LD50 <1650 mg active/kg bw.
Executive summary:

The acute oral toxicity of the test material as a 33% solution in water was assessed in male and female rats in accordance to OECD Guideline No. 401. Five male and five female rats were dosed by oral gavage with 5000 mg/kg bw (1650 mg active/kg) . After a 14 day observation period there were 8/10 mortalities. There were no treatment related effects observed on bodyweight or at gross necropsy of the remaining two male rats. The LD50 was < 1650 mg active/kg bw.

In accordance with Regulation (EC) No. 1272/2008 the substance is classified for acute toxicity by the oral route. In the absence of a derived LD50 value the substance is labelled as Category 4.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1997-09-30 to 1997-10-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague-Dawley, Indianapolis, Indiana
- Age at study initiation: 6 to 10 weeks
- Weight at study initiation: 202 - 223 g
- Fasting period before study: Yes, overnight
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
Temperature, humidity and light controlled room (DHEW publication No. 86-23 (NIH))

IN-LIFE DATES: From: 1997-09-30 To: 1997-10-14
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 33%
- Dosage volume: 0.40-0.45 g
Metal dosing cannula
Doses:
2 g/kg bw (660 mg active/kg bw)
No. of animals per sex per dose:
five males/five females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations - frequently on day of dosing (1, 2.5 and 4 hours) and once daily thereafter; bodyweights on study initiation, at 7 and 14 days post-administration and at death.
- Necropsy of survivors performed: yes
Statistics:
Calculations of the LC50 and 95% confidence limits: Method of moving averages, Weil CC (1952) table for convenient calculations of median effective dose (LD50 and ED50) and instruction in their use. Biometrics, 8.
Preliminary study:
Not performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 660 mg/kg bw
Based on:
act. ingr.
Mortality:
2/10 rats (1 male/1 female) died by Day 2 of the post-administration period. The remaining rats dosed with the test material survived until Day 14 of the post-administration period.
Clinical signs:
Loose stools were observed for 4 males and in addition two males appeared hyoactive by the Day 1 observation. One of the males showing both clinical signs of toxicity died on Day 2. The other animals showed no indications of toxicity throughout the rest of the observation period.
Hypoactivity was observed by the 4 hour observation period for one female and on Day 1 the same animal had loose stools, was prostrate and hypothermic to touch. The animal dies by Day 2. There were no clinical signs of toxicty observed in any of the other treated females.
Body weight:
Body weight of all surviving animals increased up to Day 14. However, bodyweight gain of females was reduced in comparison to males.
Gross pathology:
Occurred only in animals that died during the course of the study:
Internal observations: confined to the gastrointestinal tract, stomach and small intestine distended with gas and fluid, small intestine appeared red in colour.

Table 1: Body weight gain

Rat Number

Sex

7 day Bwt (g)

14 day Bwt (g)

587

M

283

322

588

M

276

310

589

M

267

303

590

M

258

287

591

M

-

-

592

F

216

220

593

F

229

237

594

F

250

253

595

F

-

-

596

F

218

221

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral administration of a 33% solution of the test material (2 g/kg bw) resulted in an LD50 > 660 mg active/kg bw.
Executive summary:

The acute oral toxicity of the test material as a 33% solution in water was assessed in male and female rats in accordance to OECD Guideline No. 401. Five male and five female rats were dosed by oral gavage with 2000 mg/kg bw (660 mg active/kg) . After a 14 day observation period there were 2/10 mortalities. Clinical effects were observed in three other male rats at the Day 1 observation period. No treatment related effects were noted on bodyweight gain or at gross necropsy of the surviving rats at the end of the observation period. The LD50 was > 660 mg active/kg bw.

In accordance with Regulation (EC) No. 1272/2008 the substance is classified for acute toxicity by the oral route. In the absence of a derived LD50 value the substance is labelled as Category 4.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 650 mg/kg bw
Quality of whole database:
Two guideline GLP studies are available (Klimisch score 1).

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1997-09-10 to 1997-09-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kuiper Rabitry, Gary, Indiana
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 2.01 - 2.38 kg
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
Temperature, humidity and light controlled room (DHEW publication No. 86-23 (NIH))

IN-LIFE DATES: From: 1997-09-10 To: 1997-10-24
Type of coverage:
occlusive
Vehicle:
other: moistened with water
Details on dermal exposure:
TEST SITE
- Area of exposure: 30% total body area shaved
- % coverage: 10% total body surface
- Type of wrap if used: Plastic sheeting secured with non-irritating Kendall Curity Satndard Porus tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 g/kg
- Concentration (if solution): Not applicable
- Constant volume or concentration used: yes
- For solids, paste formed: no

Duration of exposure:
24 hours
Doses:
2 g/kg
No. of animals per sex per dose:
5 male/5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: frequently on day of dosing (1, 2.5 and 4 hours) and once daily thereafter; bodyweights on study initiation, at 7 and 14 days post-administration and at death.
- Necropsy of survivors performed: yes
Statistics:
Calculations of the LC50 and 95% confidence limits: Method of moving averages, Weil CC (1952) table for convenient calculations of median effective dose (LD50 and ED50) and instruction in their use. Biometrics, 8.
Preliminary study:
Not performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
4/10 rabbits (3 male/1 female) died by Day 5 of the post-administration period. The remaining rabbits dosed with the test material survived until Day 14 of the post-administration period.
Clinical signs:
Pharmacotoxic observations were limited to the skin at the application sites and included oedema, erythema, chemical burns, scar tissue, coriaceousness and eschar. Effects were reversible by the 14 day observation period in only two animals (1 male/1 female).
Body weight:
Body weight of all surviving animals increased up to Day 14.
Gross pathology:
External observations: severe tissue damage and necrosis
Internal observations: stomach devoid of contents.

Table 1: Body weight gain

Rabbit Number

Sex

Initial Bwt (kg)

7 day Bwt (kg)

14 day Bwt (kg)

258

F

2.02

1.97

2.13

259

F

2.04

-

-

260

F

2.30

2.35

2.43

261

F

2.22

2.24

2.52

262

F

2.14

1.94

2.05

274

M

2.19

2.32

2.59

275

M

2.02

-

-

276

M

2.01

1.89

2.06

277

M

2.38

-

-

278

M

2.20

-

-

Table 2: clinical observations

Rabbit Number

Sex

Observation period

 

 

1h

2.5h

4h

Day 1

Day 2

Day 3

Day 4

Day 5

Day 6

Day 7

Day 8

Day 9

Day 10

Day 11

Day 12

Day 13

Day 14

258

F

LM

LMO

LMO

LMO

LMO

LMO

LMO

MO

OQ

OQ

OQ

Q

Q

Q

259

F

LM

LMO

LMO

X

 

 

 

 

 

 

 

 

 

 

260

F

LM

LMO

LMO

LMO

LMO

LMO

LMO

LMO

MO

O

OQ

OQ

Q

Q

261

F

LM

LMO

LMO

LMO

LMO

LMO

LMO

MO

MO

O

O

O

262

F

LM

LMO

LMO

LMO

LMO

LMO

LMO

LMO

MO

MO

O

O

OQ

OQ

274

M

LM

LMO

LMO

LMO

LMO

LMO

LMO

MO

MO

O

O

O

275

M

LMP

LMOP

LMOP

X

 

 

 

 

 

 

 

 

 

 

276

M

LM

LMO

LMO

LMO

LMO

LMO

LMO

MO

MO

MO

MO

O

OQ

OQ

277

M

LMP

LMOP

LMOP

X

 

 

 

 

 

 

 

 

 

 

278

M

LMP

LMOP

LMOP

LMOP

X

 

 

 

 

 

 

 

 

 

√ - Normal

X - Dead

L - Erythema

M - Oedema

O – Eschar and coriaceousness

P – Chemical burns

Q – Scar tissue

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal administration of the test material (2 g/kg bw) resulted in an LD50 > 2000 mg/kg bw.
Executive summary:

In this study, performed in accordance with OECD TG 402 under GLP, the substance, moistened with water, was applied to the shaved skin of rabbits (five/sex) at a dose of 2000 mg/kg bw under occlusive conditions for 24 hours. Four animals died during the 14-day observation period. No treatment related effects were noted on bodyweight gain in the remaining animals. Observations noted during the study were limited to the skin at the application sites and included erythema, edema, chemical burns, scar tissue, coriaceousness and eschar. At necropsy external observations included severe tissue damage and necrosis of skin at the application site of all four animals that died prematurely and scar tissue/scar tissue and eschar in four of the surviving animals. Two animals showed no external changes. Internally, two of the animals that died prematurely had empty stomachs. The remaining animals showed no gross internal changes. The LD50 was > 2000 mg/kg bw.

In accordance with Regulation (EC) No. 1272/2008 the substance is not classified for acute toxicity by the dermal route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
One guideline GLP study is available (Klimisch score 1).

Additional information

Acute oral toxicity

Two reliable studies are available. In the first study performed to OECD TG 401 under GLP, rats (five/sex) were dosed by gavage with 5000 mg/kg bw of a 33 %w/w solution of the substance (equivalent to 1650 mg substance/kg bw). Eight animals died during the 14-day observation period. No treatment-related effects were noted on bodyweight gain or at gross necropsy of the surviving rats at the end of the observation period. The LD50 was < 1650 mg substance/kg bw [Kukulinski M (1997a)]. In the second study performed to OECD TG 401 under GLP, rats (five/sex) were dosed by gavage with 2000 mg/kg bw of a 33 %w/w solution of the substance (equivalent to 660 mg substance/kg bw). Two animals died during the 14-day observation period. Clinical effects were observed in three other male rats at the Day 1 observation period. No treatment-related effects were noted on bodyweight gain or at gross necropsy of the surviving rats at the end of the observation period. The LD50 was > 660 mg substance/kg bw [Kukulinski M (1997b)].

Based on these two studies, the oral LD50 (rat) of the substance is between 660-1650 mg/kg bw/day.

 

 Acute inhalation toxicity

No study is available.

 

Acute dermal toxicity

One reliable study is available. In this study, performed in accordance with OECD TG 402 under GLP, the substance, moistened with water, was applied to the shaved skin of rabbits (five/sex) at a dose of 2000 mg/kg bw under occlusive conditions for 24 hours [Kukulinski M (1997c)]. Four animals died during the 14-day observation period. No treatment related effects were noted on bodyweight gain in the remaining animals. Observations noted during the study were limited to the skin at the application sites and included erythema, oedema, chemical burns, scar tissue, coriaceousness and eschar. At necropsy external observations included severe tissue damage and necrosis of skin at the application site of all four animals that died prematurely and scar tissue/scar tissue and eschar in four of the surviving animals. Two animals showed no external changes. Internally, two of the animals that died prematurely had empty stomachs. The remaining animals showed no gross internal changes. Base on the results of this study the dermal LD50 (rabbit) is > 2000 mg/kg bw.

Justification for classification or non-classification

The acute oral LD50 is between 660 and 1650 mg/kg bw, based on the results of GLP studies performed to OECD 401. The substance is therefore classified as Acute Category 4 in accordance with the criteria in Regulation (EC) No 1272/2008.

The acute dermal LD50 is > 2000 mg/kg bw, based on the results of a GLP study performed to OECD TG 401. The substance is not classified in accordance with the criteria in Regulation (EC) No 1272/2008.