Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to OECD Guidelines and to GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Cashew Nutshell Liquid (CNSL) Distilled
- Lot/batch No.: ME-0163
- Storage condition of test material: room temperature in the dark
- Other: dark amber coloured liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited
- Age at study initiation: 8-12 w eeks
- Weight at study initiation: >200 g
- Housing: individually in suspended solid floor polypropylene cages
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr): 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- % coverage: 10%
- Type of wrap if used: surgical gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): removal w ith cotton w ool moistened w ith arachis oil
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or w eight w ith unit): 2.16 ml/kg
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period follow ing administration: 14 days
- Frequency of observations and w eighing: 30 minutes, 1, 2 and 4 hours, once daily for fourteen days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body w eight, gross lesions
Statistics:
Use of statistics not indicated.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Deaths did not occur during the study.
Clinical signs:
Systemic toxicity was not observed.
Body weight:
Three females showed bodyw eight decrease or no gain in bodyw eight during the first w eek with expected gain in bodyweight during the second week. One female showed expected gain in bodyweight during the first week w ith bodyweight decrease during the second week. All males and one female show ed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities w ere noted.
Other findings:
Very slight or well-defined erythema was noted at the test sites of all animals. Other signs of dermal irritation noted were thickening of the skin, haemorrhage of dermal capillaries, hardened light brown or dark brown/black coloured scab, small superficial scattered scabs, scab undulating,scab cracking and scab lifting at edges to reveal bleeding, dried blood, glossy skin or further deep scabbing. Adverse reactions prevented accurate evaluation of erythema and oedema at all testsites during the study.

Any other information on results incl. tables

Table 2: Number of animals dead [and w ith evident toxicity] [and time range w ithin w hich mortality occurred]

Dose

(mg/kg bw)

Conc. In vehicle (%)*

Mortality (# dead/total)

Time range of deaths (hours)

Number with evident toxicity (#total)

Male

Female

Combined

Male

Female

Combined

2000

 

0/5

0/5

0/10

-

5/5

5/5

10/10

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Deaths did not occur in an acute dermal toxicity test in rats at 2000 mg/kg bw , therefore CNSL is of low acute dermal toxicity. Severe skin reactions were observed in all animals at the test substance application site.
Executive summary:

In an acute dermal toxicity study, groups of Sprague-Dawley rats (5/sex) were given a single dermal dose of CNSL distilled at 2000 mg/kg bw and observed for 14 days.

No mortality occurred in this limit test, therefore an LD50 has not been determined.

This acute study is classified as acceptable. It satisfies the guideline requirement for an acute dermal study in the rat.