Registration Dossier

Administrative data

Description of key information

Oral: LD50 > 5000 mg/kg bw

Dermal: LD50 > 2000 mg/kg bw

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:
key study
Study period:
26 Aug - 09 Sep 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted in 1987
Deviations:
yes
Remarks:
Testing was conducted in mice (rat is the preferred rodent species), only two doses were used.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
mouse
Strain:
ICR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Japan Inc., Kanagawa, Japan
- Age at study initiation: 5 weeks
- Weight at study initiation: 26 - 31 g (males); 21 - 25 g (females)
- Fasting period before study: 20 h
- Housing: After randomization, ten animals of the same sex and the same dose group were placed in a plastic cage (28 cm x 34 cm, 18 cm in depth) with shavings at the bottom. The cages were exchanged at twice per week.
- Diet: CE-2 type (Clea Japan Inc., Osaka, Japan), ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 1
- Humidity (%): 60 ± 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 or 20 mL/kg bw
Doses:
2500 and 5000 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed at 1/6, 1/2, 1, 2 and 4 hours after administration and daily (at 10 a.m.) for two weeks thereafter. Body weight of each animal was measured at 0-, 7- and 14-day of observation period.
- Necropsy of survivors performed: Yes
- Other examinations performed: Gross pathology, body weight
Statistics:
Mean body weight of treated groups was compared with the negative control by using t-test.
The incidence of gross finding in treated groups was compared with the vehicle control by using Fisher Exact test.
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:
No clinical signs of toxicity were observed up to the end of the 14-day observation period.
Body weight:
No effect on body weight was noted.
Gross pathology:
Necropsy revealed no substance-related findings.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2), and is thus sufficient to fulfill the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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:
13 Jan - 22 Mar 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted in Oct 2017
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Japan (Hino Breeding Center), Japan
- Age at study initiation: 7 weeks (males); 9 weeks (females)
- Weight at study initiation: 251.9 - 266.7 g (males); 209.8 - 224.6 g (females)
- Housing: animals were individually housed in stainless steel cages with mesh-floor (260W x 380D x 180H mm).
- Diet: pelleted diet (MF, lot No. 160915, Oriental Yeast), ad libitum
- Water: chorinated water (3 - 5 ppm by adding sodium hypochlorite to Hita City supply water), ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 25
- Humidity (%): 40 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 13 Jan 2017 To: 22 Mar 2017
Type of coverage:
semiocclusive
Vehicle:
CMC (carboxymethyl cellulose)
Details on dermal exposure:
TEST SITE
- Area of exposure: 5 x 5 cm clipped skin of the dorsal are of the trunk
- Type of wrap if used: The test material was held in contact with the skin with a non-woven gauze covered and fixed by elastic adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The non-woven gauze and elastic adhesive bandage were removed and residual test substance was removed using purified water and absorbent cotton
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 10 mL/ kg bw
- Concentration: 20% (w/v)
- Constant volume or concentration used: yes
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for signs of toxicity or mortality continuously for 10 min after the application, and were observed once 30 min and 3 h after the application. Thereafter, the animals were observed once daily from 1 to 14 days after the application.
- Necropsy of survivors performed: yes, all animals were subjected to a gross necropsy 14 days after application
- Other examinations performed: body weights were recorded prior to the application, and on day 7 and 14 after the application.
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:
2000 mg/kg bw: slight decreased spontaneous locomotion was sporadically observed in all animals of both sexes from 5 min to 3 h after the application, and disappeared after removal of the non-woven gauze and elastic adhesive bandage on the next day of the application in all animals.
Body weight:
No abnormalities were observed in any animals.
Gross pathology:
Necropsy and revealed no substance-related findings.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfill the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Acute oral toxicity

A reliable acute oral toxicity study performed with CAS 61167-58-6 similar to OECD 401 under GLP conditions was available (Laboratory of Biochemistry and Toxicology Research, 1982). In this study, groups of 10 male and female ICR mice were administered single doses of 2500 and 5000 mg/kg bw of the test substance via oral gavage. The animals were observed for 14 days after substance administration. No mortality and no clinical signs of toxicity were observed up to the end of the 14-day observation period in both dose groups. No effect on body weight was noted and necropsy revealed no substance-related findings in any dose group. In conclusion, the derived LD50 value for male and female mice was considered to be greater than 5000 mg/kg bw. Thus, based on the conducted study, CAS 61167-58-6 does not meet the classification criteria defined for acute oral toxicity according to Regulation (EC) No 1272/2008.

 

Acute dermal toxicity

The acute dermal toxicity of CAS 61167-58-6 was assessed in a limit test performed according to OECD guideline 402 and in compliance with GLP (Chemicals Evaluation and Research Institute, 2017). A group of ten rats (five/sex) was given a single, semi-occluded dermal application of the test material suspended in carboxymethyl cellulose sodium aqueous solution to the intact skin, at a dose level of 2000 mg/kg bw for 24 hours. Clinical signs and body weight development were monitored during the study. All animals were observed for 14 days and animals were subjected to gross necropsy at the end of the observation period. No mortality occurred during the study period and no abnormalities were observed at macroscopic post mortem examination in all animals. A slight decreased spontaneous locomotion was sporadically observed in all animals of both sexes from 5 min to 3 h after the application, and disappeared after removal of the non-woven gauze and elastic adhesive bandage on the next day of the application in all animals. Based on the results of this study, the LD50 value was determined to be > 2000 mg/kg bw in rats.

Justification for classification or non-classification

The available data on acute toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.