Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
From February 22, 1988 to March 24, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
KL2 due to RA
Justification for type of information:
Refer to the Quaternary ammonium salts (QAS) category or section 13 for details on the category justification. The study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Toxic Substances Control Act (TSCA) acute dermal toxicity guideline
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: slightly viscous solution
Details on test material:
- Name of test material (as cited in study report): Quaternary ammonium salts no. 1 (trimethylcocoammoniumchloride)
- Description: Clear, colourless, slightly viscous solution. This solution contained 67% water as the solvent.
Specific details on test material used for the study:
- Physical state: Clear yellow liquid
- Analytical purity: 33%
- Lot/batch No.: 1735305
- Storage condition of test material: Sealed container at room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Mochican Valley Rabbitry, Loidonville, Ohio
- Weight at study initiation: 2140 to 2990g
- Housing: individual suspended wire-mesh cages
- Diet (e.g. ad libitum): Purina Certified rabbit chow # 5322, ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: Minimum 7d

ENVIRONMENTAL CONDITIONS
- Humidity (%): 49-74%
- Photoperiod (h dark / h light): 12h / 12h

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: Shaved intact dorsal skin
- % coverage: 20%
- Type of wrap if used: Test substance was applied under gauze binders that were secured with non-irritating tape.
Duration of exposure:
24h
Doses:
0, 520, 1020 and 2000 mg/kg bw.
No. of animals per sex per dose:
Five animals per sex per test group, three animals per sex in control group.
Control animals:
yes, concurrent vehicle
Details on study design:
- Duration of observation period following administration: Animals were observed at 1, 3 and 4h post-dosing on Day 0 and twice daily for mortality and once daily for clinical observations for 14d. Application sites were examined for erythema, oedema and other dermal findings at 30−60 min after bandage removal and daily thereafter for 13 d. Erythema and oedema were graded according to Draize method.
- Frequency of observations and weighing: Day 0, 7 and 14
- Necropsy of survivors performed: yes
Statistics:
LD50 and slopes (with 95% confidence limits) were calculated by method of Litchfield and Wilcoxon.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 300 mg/kg bw
Based on:
test mat.
95% CL:
>= 800 - <= 1 900
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 900 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 500 - <= 2 400
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 600 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 200 - <= 2 100
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 429 mg/kg bw
Based on:
act. ingr.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 627 mg/kg bw
Based on:
act. ingr.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 528 mg/kg bw
Based on:
act. ingr.
Mortality:
Control: 0/6 animals
520 mg/kg bw: 0/10 animals
1020 mg/kg bw: 2/5 males and 0/5 females
2000 mg/kg bw: 4/5 males and 3/5 females
Clinical signs:
Lethargy and ataxia were the major clinical findings. Other findings included hypothermia, decreased respiratory rate, laboured respiration, nasal discharge, decreased defecation, emaciation, red staining around the mouth, diarrhoea.
Body weight:
Treatment-related body weight loss in one animal each at two higher doses throughout the 14d observation peirod. For the other eight rabbits body weight was decreased during first wk with a subsequent recovery in the second wk and net gain in the entire 14 d study period.
Gross pathology:
Treatment-related abnormality on the application sites of all rabbits. No substance-related internal abnormalities in rabbits that died during study or terminally sacrificed.
Other findings:
The test substance induced moderate to severe erythema and oedema with other significant dermal findings such as necrosis, desquamation, scabbing, eschar, exfoliation, fissuring and blenching. Subcutaneous haemorrhage was present on the application sites of one rabbit in the 2000 mg/kg bw group that survived and all animals that died.

Applicant's summary and conclusion

Interpretation of results:
other: Acute Tox. 3 based on CLP criteria
Conclusions:
Based on the results of the read across study, the acute dermal LD50 of the test substance for male and female albino rabbits was found to be 1600 mg/kg bw (95% confidence limits of 1200 − 2100 mg/kg bw) or 528 mg a.i./kg bw.
Executive summary:

A study was conducted to determine the dermal acute toxicity of the read across substance,quaternary ammonium compounds, C12-C18 (even numbered) alkyltrimethyl chloride (C12-18 TMAC), according to OECD Guideline 402 and US EPA OPP 81 -2, in compliance with GLP. The test substance (0, 520, 1020 or 2000 mg/kg bw) was applied to male and female albino rabbits under semi-occlusive conditions for 24 h. The experiment consisted of a single application to the shaved, intact skin of groups of 10 rabbits (five per sex). Animals were observed at 1, 3 and 4 h post-dosing. Following the 24 h exposure period, animals were observed for mortality, clinical signs and skin response for 14 d. There was no mortality in the control or 520 mg/kg bw group. Two males died in the 1020 mg/kg bw group while 4 males and 3 females died in the 2000 mg/kg bw group.Lethargy and ataxia were the major clinical findings. Other findings included hypothermia, decreased respiratory rate, laboured respiration, nasal discharge, decreased defecation, emaciation, red staining around the mouth, diarrhoea. Treatment-related body weight loss was recorded in one animal each at two higher doses throughout the 14 d observation period. For the other eight rabbits, body weight was decreased during first week with a subsequent recovery in the second week and net gain in the entire 14 d study period. Moreover, the test substance induced moderate to severe erythema and oedema with other significant dermal findings such as necrosis, desquamation, scabbing, eschar, exfoliation, fissuring and blenching. Subcutaneous haemorrhage was present on the application sites of one rabbit in the 2000 mg/kg bw group that survived and all animals that died. Based on the results of the read across study, the acute dermal LD50 of the test substance for male and female albino rabbits was found to be 1600 mg/kg bw (95% confidence limits of 1200 − 2100 mg/kg bw) or 528 mg a.i./kg bw (Naas, 1988).