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Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study similar to Guideline but only 4 animals (2 males/2females) per dose group used

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
only 4 animals per dose group used
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Amine KK

Test animals

Species:
rat
Strain:
other: CFY
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Interfauna UK Limited, Huntingdon, Cambridgeshire, UK
- Age at study initiation: approx. 6 - 8 weeks
- Weight at study initiation: 200 - 245 g

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
The compound was administered either unchanged at a volume of 0.63 mL/kg (= 500 mg/kg) or in water at a volume of 5 mL/kg (=2000 mg/kg).
Since the compound is described as corrosive and dermal irritative reactions were noted in the 500 mg/kg group (undiluted test material), dilution
for testing of the acute dermal toxicity at 2000 mg/kg bw is justifiable.

TEST SITE
- Area of exposure: 10% of total body surface
- % coverage: 100
- Type of wrap if used: occlusive dressing

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): 0.63 ml/kg (undiluted, 500 mg/kg group); 5 ml/kg (40% solution, 2000 mg/kg group)
- Concentration (if solution): 40% in water (only for 2000 mg/kg dose group)

VEHICLE
- water (only for 2000 mg/kg dose group)
Duration of exposure:
24h
Doses:
500 mg/kg bw (undiluted)
2000 mg/kg bw (diluted to 40% w/v in water)
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occured during the study.
Clinical signs:
500 mg/kg/bw: no clinical signs throughout observation period
2000 mg/kg/bw: hunched posture, abnormal gait (waddling), lethargy, and decreased respiratory rate (shortly after treatment, free of symptoms
thereafter)
Body weight:
Bodyweight losses were recorded on day 4 for one male and two females dosed at 500 mg/kg bw and two females dosed at 2000 mg/kg bw. Body weight gains were recorded for all other rats on day 4 and for all rats on days 8 and 15.
Gross pathology:
Terminal autopsy revealed slight bruising in the subcutaneous tissue of one male and one female rat dosed at 500 mg/kg bw and scab formation with or without ulceration was seen in all rats dosed at 2000 mg/kg bw.
An area of minimal congestion of the stomach (mucosal aspect) was seen in one female rat dosed at 2000 mg/kg bw.
Other findings:
Dermal reactions:
necrosis in all rats dosed at 500 mg/kg bw, persisting until day 12
well defined to moderate oedema in rats dosed at both levels

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute lethal dermal dose (LD 50) of Amine KK to rats was greater than 2000 mg/kg body weight
Executive summary:

In a GLP-compliant study similar to OECD TG 402, the test compound Amine KK (cocoalkylamine), a yellow liquid (purity 100%), was dermally applied under occlusion to Sprague-Dawley rats. At a dose level of 500 mg/kg body weight, the test material was applied undiluted (application volume 0.63 ml/kg bw), at a dose level of 2000 mg/kg bw the substance was diluted to a 40% solution (w/v) in distilled water (application volume 5 ml/kg). Compared to a regular OECD TG 402 study a reduced number of animals was used (4 instead of 5 animals/dose). There were no mortalities, hence, the LD50 is > 2000 mg/kg bw. No clinical signs were observed at 500 mg/kg bw. At 2000 mg/kg, hunched posture, abnormal gait, lethargy and decreased respiratory rate were noted. Signs of dermal reactions at the application site of both treatments were well defined to moderate oedema until days 4-5. Hard scabs, persisting to the end of the observation period, frequently prevented the assessment of oedema