Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Value:
185 mg/m³
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Value:
210 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.31 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Value:
65.3 mg/m³
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.75 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.75 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

Reliable and relevant data (Klimisch Code 1) are available from a Repeated Dose 90-day Toxicity Study (OECD TG408) on Distilled Grade. In the test, groups of ten male and ten female (nulliparous and non-pregnant) Wistar rats (approximately 6 weeks of age ) were allocated to a control group (no test substance) and three test substance exposure groups (i.e. doses of 50, 150 and 500 mg/kg bw/day. The test substance and vehicle were administered to the appropriate animals by once daily oral gavage 7 days a week for a minimum of 90 days, up to and including the day before scheduled necropsy. Clinical signs, functional observations, body weight development and food and water consumption were monitored during the study.

 

Exposure to Distilled Grade did not result in adverse effects in rats at levels of 50 and 150 mg/kg bw/day. Histopathological examinations showed epithelial hyperplasia of the non-glandular mucosa of the stomach (forestomach, squamous mucosa) at 50, 150 and 500 mg/kg bw/day in males and females with a dose-related increase in severity, up to marked in males and moderate in females. At 150 and 500 mg/kg bw/day this correlated with macroscopically irregular stomach surfaces. These findings at 500 mg/kg bw/day were interpreted to be adverse due to the overall severity and concurrent presence of ulceration in some animals. Furthermore, a lower body weight gain was observed in males at 500 mg/kg bw/day which was also considered to be adverse. Other test substance-related changes in clinical signs, body weight, clinical pathology, organ weights and histopathology were considered non-adverse. This included an assessment of the absolute weights of a series of reproductive organs/tissues (testes, epididymides, prostate gland and seminal vesicle in males and ovary and uterus in females) which showed that there were no changes, relative to those in the controls, at any exposure dose. However, when the results were adjusted relative to the terminal body weights of the rats small, but statistically significant increases in the weight of the testis (20%) and the epididymis (18%), relative to body weight, were evident in males exposed to 500 mg/kg bw/day when compared to measurements made on the controls. Histopathological examination of the organs/tissues in males and females showed that none of the reproductive organs/tissues in males and females showed observable changes compared to those from the control animals indicating that prolonged exposure did not affect the male and female reproductive systems.

 

Based on the results generated a No Observed Adverse Effect Level (NOAEL) for the systemic toxicity of Distilled Grade of 150 mg/kg bw/day was established. This NOAEL also provides protection against the observed local effects on stomach morphology due to the known irritancy of the test substance.

The key data from the OECD TG408 Repeated Dose 90-day Toxicity Study is supported by information from a well conducted oral study combining a repeat dose toxicity study with reproduction/developmental toxicity screening has been performed in the rat using Cashew Nutshell Extract, Decarboxylated, Distilled (Distilled Grade). A sub-acute (short-term) No Observed Adverse Effect Level (NOAEL) of 150 mg/kg bw/day has been identified from this study.

 

Only limited information on the toxicokinetics and toxicodynamics of Cashew Nutshell Extract, Decarboxylated Distilled (Distilled Grade) are available based on inference from the available test data, Therefore assessment (uncertainty) factors for interspecies

and intraspecies variation cannot be specifically derived, and therefore, default factors as prescribed in the ECHA guidance have been used