Reaction mass of Benzenepropanal, 4-ethyl-α,α-dimethyl- and 3-(2-ethylphenyl)-2,2-dimethylpropanal

Endpoint summary

Description of key information

Acute oral toxicity: OECD TG 401: LD50 > 5000 mg/kg bw

Acute inhalation toxicity: Extrapolated from acute oral toxicity LC50 > 13000 mg/m3

Acute dermal toxicity: OECD TG 402: LD50 > 5000 mg/kg bw

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

Study period:

23 July 1980 to 6 August 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals
- Age at study initiation: 8 weeks
- Weight at study initiation: 221 – 250 g
- Fasting period before study: 16 – 20 hours
- Housing: animals were housed 5 per cage in suspended wire mesh cages
- Diet: fresh Purina rat chow, ad libitum
- Water: ad libitum
- Acclimation period: at least one week

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: animals were observed 3-4 hours after dosing and once daily for 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

4 out of 10 animals exposed to 5000 mg/kg bw died.

Clinical signs:

other: Lethargy was noted in 5 animals on day 1. Oily anogenital area was noted in 5 or more animals on day 1 and 2. The survivors were normal until day 11 and 12 when piloerection was noted in several animals. Ptosis was noted in 1 animal on day 13. The survivi

Gross pathology:

- No effects were observed in the animals that were sacrificed on day 14.
- Stained brown anogenital area, congested lung, dilated heart, excess fluid in pleural cavity, stomach and intestines distended, intestines grey and/or purple and pale exudate contained in pleural cavities and pericardium were observed in animals that died.

Interpretation of results:

other: Not acute harmful

Remarks:

in accordance with CLP (1272/2008 and its updates)

Conclusions:

The acute oral toxicity test showed a LD50 of > 5000 mg/kg bw

Executive summary:

In a GLP compliant study, performed similar to OECD TG 401, ten male Wistar rats were exposed to the test substance via oral gavage. Animals received a dose of 5000 mg/kg bw. After an observation period of 14 days animals were necropsied. 4 out of 10 ten animals exposed died. Lethargy and oily anogenital area was noted in 5 or more animals. The survivors were normal until day 11 and 12 when piloerection was noted in several animals. Ptosis was noted in 1 animal on day 13. The surviving animals were normal on day 14. No effects were observed upon necropsy in the animals that were sacrificed on day 14. Stained brown anogenital area, congested lung, dilated heart, excess fluid in pleural cavity, stomach and intestines distended, intestines grey and/or purple and pale exudate contained in pleural cavities and pericardium were observed in animals that died. The LD50 was determined to be higher than 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The acute oral toxicity result is of sufficient quality and adequate for this dossier.

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:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6 Aug 1980 to 30 Sep 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Perfection Breeders, Nicholas Helf
- Age at study initiation: 8 weeks
- Weight at study initiation: 2.0 – 2.8 kg
- Housing: animals were housed 2 animals per cage in suspended wire mesh cages
- Diet: fresh Purina rabbit chow, ad libitum
- Water: ad libitum
- Acclimation period: at least one week

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: immediately prior to dosing, the fur was clipped from the abdomen. Abrasions were made in ½ of the rabbits. The abrasions, extending the length of the exposure site, scratched the stratum corneum but did not reach the derma or produce bleeding. The test material was applied once to the prepared site under gauze patches.
- % coverage: The clipped area was 200 cm2, approximately 10% of the body surface.
- Type of wrap if used: Patches were secured with adhesive tape and the trunks were wrapped with impervious material.

REMOVAL OF TEST SUBSTANCE
- Washing: the exposure site was wiped, but not washed
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 5000 mg/kg bw

Duration of exposure:

24 hours

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

6 males and 4 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Dermal reactions were scored at 1, 7 and 14 days after exposure. Animals were observed daily for signs of toxicity, pharmacological effects and mortality.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: Animals were in generally good health.

Gross pathology:

Internal organs, on superficial examination, appeared normal.

Other findings:

Skin reactions were generally slight on days 1 and 7 and generally cleared by day 14. One animal had severe edema on day 1 and crusted skin at necropsy on day 14. Scaly skin was observed in 6 out of 10 animals at necropsy.

Interpretation of results:

other: Not acute harmful

Remarks:

in accordance with EU CLP (EC 1272/2008 and its updates)

Conclusions:

The acute dermal toxicity test showed an LD50 > 5000 mg/kg bw

Executive summary:

In a GLP compliant study, similar to OECD TG 402, ten New Zealand White rabbits were exposed to the test substance via dermal application. Six males and four females were exposed to 5000 mg/kg bw. After an observation period of 14 days animals were necropsied. All animals survived the study in generally good health. Changes in body weights were generally normal. Internal organs, on superficial examination, appeared normal.Skin reactions were generally slight on days 1 and 7 and generally cleared by day 14. One animal had severe edema on day 1 and crusted skin at necropsy on day 14. Scaly skin was observed in 6 out of 10 animals at necropsy. The LD50 was determined to be higher than 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The acute dermal toxicity result is of sufficient quality and adequate for this dossier.

Additional information

Acute Oral toxicity

In a GLP compliant study, performed similar to OECD TG 401, ten male Wistar rats were exposed to the test substance via oral gavage. Animals received a dose of 5000 mg/kg bw. After an observation period of 14 days animals were necropsied. 4 out of 10 ten animals exposed died. Lethargy and oily anogenital area was noted in 5 or more animals. The survivors were normal until day 11 and 12 when piloerection was noted in several animals. Ptosis was noted in 1 animal on day 13. The surviving animals were normal on day 14. No effects were observed upon necropsy in the animals that were sacrificed on day 14. Stained brown anogenital area, congested lung, dilated heart, excess fluid in pleural cavity, stomach and intestines distended, intestines grey and/or purple and pale exudate contained in pleural cavities and pericardium were observed in animals that died. The LD50 was determined to be higher than 5000 mg/kg bw.

Acute inhalation toxicity

The acute inhalation toxicity for the substance can be derived using data on the acute oral toxicity using the following methodology: CLP guidance (2015 3.1.6.1.8. Example 8, page 268): using the extrapolation formula 1 mg/kg bw = 0.0052 mg/L/4h. The LD50 of the substance for acute oral toxicity is > 5000 mg/kg bw. This 5000 mg/kg bw can be converted to > 26 mg/L = 26 gram/m3. Taking into account the inhalation absorption as 100% and oral absorption 50%, the acute inhalation toxicity would become >13000 mg/m3. The saturated vapour pressure of the substance is: 33 mg/m3 (0.43 Pa (Vap Pr. Floralozone) x 190 (MW) / 8.3 (R, gas constant) x 297 (°K) x 1000 (conversion of grams to mg). This means that the acute inhalation LC50 > 13000 mg/m3 cannot be reached because it exceeds the saturated vapour pressure by more than a factor of almost 400.

Acute dermal toxicity

In a GLP compliant study, similar to OECD TG 402, ten New Zealand White rabbits were exposed to the test substance via dermal application. Six males and four females were exposed to 5000 mg/kg bw. After an observation period of 14 days animals were necropsied. All animals survived the study in generally good health. Changes in body weights were generally normal. Internal organs, on superficial examination, appeared normal. Skin reactions were generally slight on days 1 and 7 and generally cleared by day 14. One animal had severe edema on day 1 and crusted skin at necropsy on day 14. Scaly skin was observed in 6 out of 10 animals at necropsy. The LD50 was determined to be higher than 5000 mg/kg bw.

Justification for classification or non-classification

Based on the available information classification and labelling for acute oral, dermal and inhalation toxicity is not warranted in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008 and its amendments.