Ethylenebis(oxyethylene) bis[3-(5-tert-butyl-4-hydroxy-m-tolyl)propionate]

Endpoint summary

Description of key information

The substance is of low toxicity after single oral administration to rats and hamsters. No mortality and no signs of toxicity were observed in a study for acute dermal toxicity in rats.

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:

From Aug. 28, 1979 to Oct. 31, 1979

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

yes

Remarks:

(individual data were not presented; justification for choice of vehicle was not provided; light/dark cycle was 10/14 instead of 12/12, dose level too high).

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: Tif: RAIf

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Raised on the premises of CIBA-GEIGY Ltd. Exp. Toxicology Sisslen
- Age at study initiation: (7 to 8 weeks old)
- Weight: not reported
- Housing: housed in groups of 5 in macrolon cages type 3
- Fasting period before study: yes
- Diet and water: ad libitum rat food -NAFAG, Gossau SG ~ and water.
- Acclimation period: a minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Photoperiod (hrs dark / hrs light): 14/10

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 20 mL/kg body weight

Doses:

4000, 5000, 6000, or 7000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weights measured on days 1, 7 and 14; mortality measured at 1,2,3,5, and 24 hours after dosing and from day 2 to 14
- Necropsy of survivors performed: yes

Statistics:

LD50 including 95 % confidence limits are calculated by the logit model

Preliminary study:

not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 7 000 mg/kg bw

Mortality:

1 male in the 5000 group died 4 days after dosing

Clinical signs:

other: Sedation, Dyspnoea, Exophthalmos, Ruffled fur, Diarrhoea and curved body position were observed, reversible within 8 days.

Gross pathology:

no findings

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of the test item in rats observed over a period of 14 days is greater than 7000 mg/kg for both sexes. The test material has therefore practically no acute toxicity to the rat by this route of administration.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

7 000 mg/kg bw

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:

experimental study

Adequacy of study:

key study

Study period:

From Apr. 1, 1992 to Jun. 22, 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Limited (Animal Production) 4332 stein, Switzerland
- Weight at study initiation: 202 to 229 g
- Housing: Individually housed, in Macrolon cages type 3, with standarized soft wood bedding
- Diet: ad libitum, NAFAG 890 TOX
- Water: ad libitum
- Acclimation period: 5 days

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

IN-LIFE DATES: From May 21, 1992 to June 4, 1994.

Type of coverage:

semiocclusive

Vehicle:

CMC (carboxymethyl cellulose)

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: 10%
- Type of wrap if used: guaze-lined semiocclusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cleaned with lukewarm water
- Time after start of exposure: 24 hour

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Constant volume or concentration used: yes (4 mL/kg body weight)

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5% carboxymethylcellulose in 0.1% aqueous polysorbate 80

Duration of exposure:

24 hours

Doses:

2,000 mg/kg body weight

No. of animals per sex per dose:

5 animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations and weighing on Day 0, 7 and 14
- Necropsy of survivors performed: yes

Statistics:

None

Preliminary study:

Limit Test

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality

Clinical signs:

other: Piloerection was seen, that is a common unspecific clinical sign in acute dermal tests. The animals recovered within 2 to 3 days. At autopsy, no deviations from normal morphology were found.

Gross pathology:

None

Other findings:

Other Observations: No deviation from normal morphology were found upon necropsy

Interpretation of results:

GHS criteria not met

Executive summary:

Upon an acute dermal administration of 24 hours and a 14 day post-treatment observation period, the following LD50 (with 95% confidence limits calculated, where possible) was determined for the test item:

LD50 in male rats: greater than 2000 mg/kg body weight

LD50 in female rats: greater than 2000 mg/kg body weight

LD50 in rats of both sexes: greater than 2000 mg/kg body weight

Piloerection was seen, being a common symptom in acute dermal tests. The animals recovered within 2 to 3 days. At autopsy, no deviations from normal morphology were found.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity

Acute oral toxicity in rats was investigated in a study similar to OECD testing guideline 423. It was not performed under GLP and no individual data is reported. Rats were given a single dose of 4000, 5000, 6000 or 7000 mg/kg bw using polyethylene glycol as vehicle. One male rat in the dose group of 5000 mg/kg bw died four days after dosing. Sedation, Dyspnoea, Exophthalmos, Ruffled fur, diarrhoea and curved body position were observed, during the first 7 days. There were no significant changes in body weight gain and no adverse findings upon necropsy. Based on these results, the LD50 in rats after oral application is greater than 7000 mg/kg body weight. This result is supported by a study in Chinese hamster which was performed with a limit dose of 3000 mg/kg bw. It was not performed under GLP but followed the procedure of OECD testing guideline 423. No mortality and no adverse signs of toxicity were recorded. Dyspnoea, curved body position and ruffled fur were observed during the first 11 days. Based on these findings, the oral LD50 in hamsters is greater than 3000 mg/kg body weight.

Acute dermal toxicity

Acute dermal toxicity was investigated in rats in a GLP and OECD 402 compliant guideline study. No mortality and no indication of toxicity was observed at the limit dose of 2000 mg/kg bw.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute oral and dermal toxicity under Regulation (EC) No. 1272/2008.