2-hydroxy-1-[4-[4-(2-hydroxy-2-methylpropanoyl)phenoxy]phenyl]-2-methylpropan-1-one

Endpoint summary

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:

16 Sep - 14 Oct 2004 (experimental period)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratoires, L'Arbresle Cedex, France.
- Females nulliparous and non-pregnant: yes .
- Age at study initiation: 8-12 weeks at the time of administration.
- Weight at study initiation: Within ± 20% of the mean weight of any previously dosed animals.
- Fasting period before study: yes, deprived of food since the previous day.
- Housing: Daily observations were performed at the time of delivery of the animals and during the period of acclimatization. Animals were housed in cages of standard dimensions with sawdust bedding (or equivalent). Cages were cleaned at least once per week. The animals were placed in an air-conditioned (19-23°C) animal house kept at relative humidity between 45% and 65% in which non-recycled filtered air was changed approximately 10 times per hour. The artificial day/night cycle involved 12 hours light and 12 hours darkness with light on at 7.30 a.m.
- Diet (e.g. ad libitum): RM1 (E)-SQC SDS/DIETEX feed (quality controlled/radiation sterilised) was available ad libitum (except during the fasting experimental period). The criteria for acceptable levels of contami­nants in the feed supply were within the limits of the analytical specifications established by the diet manufacturer.
- Water (e.g. ad libitum): Drinking water was available ad libitum in polycarbonate feeder bottles with a stainless steel nipple. A specimen of water is obtained every 6 months and sent to a laboratory for analysis. The criteria for acceptable levels of contaminants in the water supply were within the limits of the analytical specifications.
- Acclimation period: Minimum of five days before treatment in the laboratory animal house where the experiment took place.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

- Vehicle: sterile water
- dose volume applied: 10mL/kg

Doses:

2000 mg/kg bw (limit test; at request of the sponsor)

No. of animals per sex per dose:

6 females

Control animals:

no

Preliminary study:

-

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no 95% CL stated

Mortality:

There were no deaths.

Clinical signs:

other: No clinical signs were observed from D1 to D14 during the course of the first step of the study. On D1 (about 3 hours 30 minutes post-dosing), all females presented a piloerection during the second step of the study. No clinical signs were observed from D

Gross pathology:

No organ or tissue gross findings were seen at necropsy

Other findings:

none

Interpretation of results:

other: EU-GHS criteria not met

Conclusions:

LD50 > 2000 mg/kg bw

Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance in female SD rats according to OECD Guideline 423, in compliance with GLP. At the first step, a group of three females was treated with the starting dose of 2000 mg/kg bw, followed by an additional group of three animals at the same dose level. The test substance was administered orally to animals deprived of food since the previous day, in a volume of 10 mL/kg as a white homogeneous suspension in sterile water. The rats were monitored daily for 14 days after administration of the test substance. Bodyweight was recorded on Days 1, 7, 14 and 15. No mortality occurred during the study. No clinical signs were observed from Day 1 to 14 in the first step of the study. On Day 1 (about 3.5 h post-dosing), all females presented piloerection during the second step of the study. No further clinical signs were recorded. Mean bodyweight gain in treated animals was within the expected normal range. No organ or tissue gross findings were seen at necropsy. Under the study conditions, the acute oral LD50 of the test substance in rats was greater than 2000 mg/kg bw (Baudet, 2004).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral 

 

A study was conducted to determine the acute oral toxicity of the test substance in female SD rats according to OECD Guideline 423, in compliance with GLP. At the first step, a group of three females was treated with the starting dose of 2000 mg/kg bw, followed by an additional group of three animals at the same dose level. The test substance was administered orally to animals deprived of food since the previous day, in a volume of 10 mL/kg as a white homogeneous suspension in sterile water. The rats were monitored daily for 14 days after administration of the test substance. Bodyweight was recorded on Days 1, 7, 14 and 15. No mortality occurred during the study. No clinical signs were observed from Day 1 to 14 in the first step of the study. On Day 1 (about 3.5 h post-dosing), all females presented piloerection during the second step of the study. No further clinical signs were recorded. Mean bodyweight gain in treated animals was within the expected normal range. No organ or tissue gross findings were seen at necropsy. Under the study conditions, the acute oral LD50 of the test substance in rats was greater than 2000 mg/kg bw (Baudet, 2004).  

  

Dermal 

 

The study does not need to be conducted because the substance does not meet the criteria for classification for acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo skin irritation or skin sensitization studies using dermal exposure.  

  

Inhalation 

 

According to REACH Annex VIII column 2, 8.5.2., testing by the inhalation route is appropriate if exposure of humans via inhalation is likely, considering the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles, or droplets of an inhalable size. This is not the case since the estimated vapour pressure of the substance is 1.44E-9 Pa at 25°C and, as it is a solid, no droplets of inhalable size will be formed. Therefore, no acute oral inhalation testing was conducted.

Justification for classification or non-classification

Based on the results of an acute oral toxicity test (OECD Guideline 423), the test substance does not meet the CLP classification criteria for this endpoint, as set out in Regulation (EC) No. 1272/2008.