Registration Dossier

Administrative data

Description of key information

Oral, inhalation and dermal acute toxicity are all considered.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
No information.
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Study is old data conducted to no recognised test guideline. The data are reported in a brief resume of the test and observations.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Test substance was administered orally as supplied by the sponsor to 5 male and 5 female rats. The method of dosing is not reported.

GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
Not reported.
Route of administration:
other: no data.
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Single dose of 5000 mg/kg administered as received. No other data included.
Doses:
5000 mg/kg
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
no
Details on study design:
No data.
Statistics:
No data.
Preliminary study:
No data.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
95% CL:
>= 7 - <= 46
Mortality:
One animal on Day 1 and two animals on Day 2 died
Clinical signs:
No data.
Body weight:
Average bodyweight gain for male animals was 44g and the average bodyweight gain for female animals was 29g.
Gross pathology:
No data.
Other findings:
None

Mortality data

Dose level mg/kg

No. rats dosed

deaths per day

Mortality after 14 days

1

2

3

4

5

6

7

8

9

10

11

12

13

14

5000

10

1

2

0

0

0

0

0

0

0

0

0

0

0

0

3/10

Individual bodyweight data

Dose Level mg/kg

Animal No. & sex

Body weights (g)

Initial

14 Days

5000

021M

275

280

 

022M

264

320

 

023M

357

397

 

024M

273

---

 

025M

268

325

 

Average

287

311

5000

026F

186

215

 

027F

180

---

 

028F

210

235

 

029F

205

---

 

030F

190

220

 

Average

194

223

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance demonstrated a 30% mortality rate and has been completed as a limit test at 5000 mg/kg The LD50 is considered to be >5000 mg/kg.

Executive summary:

The test sample was dosed orally to 5 male and 5 female rats at a dose of 5000 mg/kg. Assessed over a 14 day period, 1 male and 2 female deaths occured and the study was completed as a limit test. The LD50 is considered >5000 mg/kg.

No classification is applicable on the basis of the results.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw
Quality of whole database:
K3-study not conducted to GLP or in compliance with agreed protocols.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1975, not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non GLP, not carried out according to recognised guideline, although results documented.
Qualifier:
according to
Guideline:
other: as outlined i n 16 CFR 1500.3
Deviations:
not specified
Principles of method if other than guideline:
Test substance was administered by inhalation as supplied by the sponsor and aerosolised to 5 male and 5 female rats. Ten adult albino rats (wistar-derived strain ) equally distributed into five males and five females weighing between 200-300g were exposed to the test material administered as a volume of gas or vapor for one hour in an all glass (72 liter) chamber under the following conditions :

Air Flow: 10 liters per minute
Weight of material aerosolized: 2 g/minute
Nominal concentration of test material: 200 mg per Liter
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
The test utilised ten adult albino rats (wistar-derived strain ) equally distributed into five males and five females weighing between 200-300g. No other information is detailed.
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Ten adult albino rats (wistar-derived strain ) equally distributed into five males and five females weighing between 200-300g were exposed to the test material administered as a volume of gas or vapor for one hour in an all glass (72 liter) chamber under the following conditions :
Air Flow: 10 liters per minute
Weight of material aerosolized: 2 g/minute
Nominal concentration of test material: 200 mg per Liter
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
1 h
Concentrations:
200 mg/l
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
no
Details on study design:
Ten adult albino rats (wistar-derived strain ) equally distributed into five males and five females weighing between 200-300g were exposed to the test material administered as a volume of gas or vapor for one hour in an all glass (72 liter) chamber under the following conditions :
Air Flow: 10 liters per minute
Weight of material aerosolized: 2 g/minute
Nominal concentration of test material: 200 mg per Liter
Statistics:
None
Preliminary study:
Not applicable.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 200 mg/L air
Based on:
test mat.
Exp. duration:
1 h
Mortality:
1 death on Day 7.
Clinical signs:
No data.
Body weight:
No data.
Gross pathology:
No findings.
Other findings:
No acute symptoms were observed prior: to death. Gross examination at autopsy of the one animal that died revealed no noteworthy findings.

Mortality data

Dose level mg/l

No. rats dosed

deaths per day

Mortality after 14 days

1

2

3

4

5

6

7

8

9

10

11

12

13

14

200

5M

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/5

 

200

5F

0

0

0

0

0

0

1

0

0

0

0

0

0

0

1/5

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance demonstrated a 10% mortality rate and has been completed as a limit test at 200 mg/l The LD50 is considered to be >200 mg/l.
Executive summary:

The test sample was dosed by inhalation to 5 male and 5 female rats at a dose of 200 mg/l. Assessed over a 14 day period, 0 male and 1 female deaths occurred and the study was completed as a limit test. The LC50 is considered >200 mg/l.

 

No classification is applicable based on the results.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
200 mg/m³
Quality of whole database:
K2-study not conducted to GLP or in compliance with agreed protocols.

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:
1975, not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non GLP, not carried out according to recognised guideline, although results documented.
Qualifier:
according to
Guideline:
other: 16 CFR 1500. 40
Deviations:
not specified
Principles of method if other than guideline:
The acute dermal toxicity study (single exposure) was conducted on adult albino rabbits selected from healthy, acclimated animals, as described in 16 CFR 1500. 40. No other information is specified.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
other: Albino
Sex:
not specified
Details on test animals and environmental conditions:
The acute dermal toxicity study (single exposure) was conducted on adult albino rabbits selected from healthy, acclimated animals, as described in 16 CFR 1500. 40. No other information is specified.
Type of coverage:
not specified
Vehicle:
not specified
Details on dermal exposure:
No data.
Duration of exposure:
14 days.
Doses:
10000 mg/kg
No. of animals per sex per dose:
No data.
Control animals:
not specified
Details on study design:
No data.
Statistics:
No data.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths.
Clinical signs:
No data.
Body weight:
No data.
Gross pathology:
No data.
Other findings:
None

Mortality data

Dose level mg/kg

No. rabbits dosed

deaths per day

Mortality after 14 days

1

2

3

4

5

6

7

8

9

10

11

12

13

14

10000

5 (Intact skin)

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/5

 

10000

5 (Abraded skin)

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/5

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance demonstrated a 0% mortality rate and has been completed as a limit test at 10000 mg/kg. The LD50 is considered to be >10000 mg/kg.
Executive summary:

The test sample was dosed dermally to 5 animals with intact skin and 5 animals with abraded skin at a dose of 10000 mg/kg. Assessed over a 14 day period, 0 deaths occured and the study was completed as a limit test. The LD50 is considered >10000 mg/kg.

No classification is applicable based on the results.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
10 000 mg/kg bw
Quality of whole database:
K2-study not conducted to GLP or in compliance with agreed protocols.

Additional information

Testing on the above endpoints gave the following results:

 

Acute toxicity: Oral.

 

3 studies are available for the derivation of LD50 acute oral toxicity as follows:

 

LD 50: > 5000 mg/kg

 

LD 50: > 20000 mg/kg

 

LD 50: 21 ml/kg bodyweight 

 

All 3 studies are considered to be lacking in certain data requirements; however despite being studies conducted at different times there is an equivalent toxicological profiles and value as not hazardous for this endpoint. Hence, on the basis of a weight of evidence approach, it is considered that applicable of oral LD50 values results in no classification. A fourth study offered as supporting information are not considered relevant given that definitive values have been obtained in the first 3 studies.

 

Acute toxicity: Dermal.

 

Two main studies are presented for this endpoint as follows:

 

LD50: >10000 mg/kg

 

LD50: >200 mg/kg

 

Both studies conducted at different times show equivalent toxicological profiles and values; hence it is considered that application of the LD50 values results in no classification. 

 

Acute toxicity: Inhalation.

 

 Two studies are again presented for this endpoint as follows:

 

LC50 (1-hour): >200 mg/l (air)

 

LC 50 (1-hour) 2 mg/l (air)

 

Neither study in isolation is suitable for hazard assessment for this endpoint; however given the low volatility of the substance, extensive exposure by inhalation is not anticipated. There is the potential for exposure by inhalation from some of the categories of use; however as these are as a result of the substance as a component of a product at low level, plus the fact that PPE during use of such products is recommended, it is considered that exposure by inhalation will not pose a hazard. In addition, the dermal route of exposure is considered more appropriate for exposure to the substance, given the nature and conditions of usage.

Justification for classification or non-classification

The above studies have all been ranked reliability 2 or 3 according to the Klimisch et al system. This ranking was deemed appropriate because the studies were not conducted to GLP or in compliance with agreed protocols. The reports do not detail a specific method; however these document dose levels and responses in detail, so is deemed appropriate for use in the support of a formal registration. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

Justification for classification or non classification

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for acute effects is therefore required.