Fatty acids, C16-18 and C18-unsatd., reaction products with glycidyl neodecanoate and 7-oxabicyclo[4.1.0]hept-3-ylmethyl 7-oxabicyclo[4.1.0]heptane-3-carboxylate

Endpoint summary

Description of key information

The oral LD50 value in rats is greater than 2000 mg/kg bw. This limit value allows the conclusion that dermal and inhalation toxicity are unlikely.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Guideline study under GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Velaz Province, Czech Republic
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 180-200 g
- Fasting period before study: Overnight
- Housing: plastic cages, 3 animals/cage, bedding: Lignocel S3/4
- Diet (e.g. ad libitum): ad lib, altromin
- Water (e.g. ad libitum): ad lib, tap water (certificate of analysis available)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 ˚C
- Humidity (%): 55 +/- 10
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2016/03/10 To: 2016/03/30

Route of administration:

oral: gavage

Vehicle:

olive oil

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Immediately after administration, 0.5, 1.0, 2, and 4.0 hours after administration. Further observed once daily for 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behaviour patterns. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep, and coma.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality during 14 day study period

Clinical signs:

other: There were no observed clinical signs

Gross pathology:

No gross pathology was observed during 14 day study period

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of the test material is > 2000 mg/kg bw in the Wistar rat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

adequate

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

The study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size [exposure considerations]. Furthermore, according to Annex VIII, Section 8.5, Column 2, of Regulation EC No. 1907/2006, a toxicity study, in addition to the acute oral toxicity study, under 8.5.2 to 8.5.3 shall be provided for at least one other route. Regulation EC No. 863/2016 amends this data requirement, stating that substances that are not toxic via the oral route may be expected with high certainty to be also non-toxic via the dermal route. The risk of acute toxicity by the dermal route has been addressed in light of an acute oral toxicity study with a LD50 > 2000 and no systemic toxicity observed in other in vivo studies. It is determined that testing for acute dermal toxicity is not scientifically indicated. The criteria for satisfaction of Sections 8.5.2 and 8.5.3 are met and the data requirement for an acute toxicity study by a third route, inhalation, is waived.

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

adequate

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

According to Regulation EC No. 863/2016 amending Regulation EC No. 1907/2006, acute testing by the dermal route does not need to be conducted if the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route, and no systemic effects have been observed in in vivo studies with dermal exposure. The test material displayed an acute oral LD50 > 2000 mg/kg bw in rats, is not classified as STOT SE, and no systemic toxicity or local irritation was observed in a LLNA study in mice. Therefore the substance meets the criteria for waiving the testing requirements for acute dermal toxicity.

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

adequate

Additional information

The acute inhalation toxicity study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size [exposure considerations]. Furthermore, according to Annex VIII, Section 8.5, Column 2, of Regulation EC No. 1907/2006, a toxicity study, in addition to the acute oral toxicity study, under 8.5.2 to 8.5.3 shall be provided for at least one other route. Regulation EC No. 863/2016 amends this data requirement, stating that substances that are not toxic via the oral route may be expected with high certainty to be also non-toxic via the dermal route. The risk of acute toxicity by the dermal route has been addressed in light of an acute oral toxicity study with a LD50 > 2000 and no systemic toxicity observed in other in vivo studies. It is determined that testing for acute dermal toxicity is not scientifically indicated. The criteria for satisfaction of Sections 8.5.2 and 8.5.3 are met and the data requirement for an acute toxicity study by a third route, inhalation, is waived.

Justification for classification or non-classification

The criteria for classification for acute toxicity, according to Regulation EC No. 1272/2008, are not met, and the substance is not classified.