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Administrative data

Description of key information

Information from the repeat dose and reproductive toxicity screening test on the read across substance Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade)demonstrate low sub-acute oral toxicity and can be used to infer low acute toxicity. In the combined repeated dose/reproductive toxicity screening test, serious adverse effects are not observed with oral dietary doses of up to 1000 mg/kg bw/day, following dosing for 54 consecutive days. On this basis it was not considered appropriate to test for acute oral toxicity, as absence of severe adverse effects at this dose following repeated dosing indicates that mortality is unlikely to occur after a single dose in an acute oral toxicity test at doses that would trigger classification. A limit dose test of 2000 mg/kg bw/day can be waived, as no further information on hazard class would be generated. Limit tests are usually required by regulatory regimes when a substance is not expected to be toxic. However, REACH allows for waiving of tests where the hazard and risk of a substance can be inferred by alternative means. Expert judgement can, therefore, be exercised to waive the acute oral toxicity test, based on a weight of evidence approach. In an acute dermal toxicity study, groups of Sprague-Dawley rats (5/sex) were given a single dermal dose of read across substance Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) at 2000 mg/kg bw and observed for 14 days. Deaths did not occur in this study, therefore, it can be determined that Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) is of low acute dermal toxicity. Severe skin reactions were observed in all animals at the test substance application site. Exposure of humans to Cashew Nutshell Extract, Decarboxylated, (Distillation Residue Grade) via inhalation is not likely, taking into account the vapour pressure of the substance and the low possibility of exposure to aerosols, particles or droplets of an inhalable size.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted to OECD Guidelines and to GLP.
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
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 weeks
- Weight at study initiation: >200 g
- Housing: individually in suspended solid floor polypropylene cages
- Diet (e.g. ad libitum): ad libitum
- 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
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 with cotton wool moistened with arachis oil
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with 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 following administration: 14 days
- Frequency of observations and weighing: 30 minutes, 1, 2 and 4 hours, once daily for fourteen days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross lesions
Statistics:
Use of statistics not indicated.
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 bodyweight decrease or no gain in bodyweight during the first week with expected gain in bodyweight during the second week. One female showed expected gain in bodyweight during the first week with bodyweight decrease during the second week. All males and one female showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were 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 test sites during the study.

Table 2: Number of animals dead [and with evident toxicity] [and time range within which 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

 

Read across justification - A document which justifies the read–across from Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distilled (“Distilled Grade”) to Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distillation Residue (“Distilled Residue Grade”) is attached in the endpoint summary.

 

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Deaths did not occur in an acute dermal toxicity test in rats at 2000 mg/kg bw, therefore Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) 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 Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) 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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

For the assessment of acute toxicity the read across substance is Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distilled (“Distilled Grade”).

A document which justifies the read–across from Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distilled (“Distilled Grade”) to Cashew (Anacardium occidentale) Nutshell Extract, Decarboxylated, Distillation Residue (“Distilled Residue Grade”) is attached.

Justification for classification or non-classification

An LD50 of >2000 mg/kg bw was idenitified from an acute dermal toxicity study, therefore read across substance Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade) is of low acute dermal toxicity and does not warrant classification under the DSD. However, classification with category 4, harmful in contact with skin, is appropriate under CLP.

Inflammation from a sub-acute repeat dose toxicity combined screening test infers that effects do not occur at doses up to 1000 mg/kg bw/day, therefore, classification is not warranted under the DSD. However, classification with category 4, harmful in contact with skin, is appropriate under CLP.

No data are available to classify the acute inhalation effects.