Ethyl 4-hydroxybenzoate

Endpoint summary

Description of key information

Oral (OECD 401), rat: LD50 > 3100 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:

3.8. - 6.9.1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions. Necropsy was not performed in all surviving animals. Not performed according to GLP. No analytical purity was given in the study report.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Necropsy was not performed in all surviving animals; no data on analytical purity was given.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Wistar (BOR:WISW)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: 9 - 14 weeks
- Weight at study initiation: 162 g (males), 170 g (females)
- Fasting period before study: Animals were fasted from 16 h before application until 4 h after application. During this period tap water was available.
- Housing: Groups of five animals were housed in Makrolon cages type III with dustfree wood pellets as bedding material.
- Diet: Altromin R 1324, Altromin GmbH, Germany, ad libitum
- Water: tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1,5
- Humidity (%): 60 ± 5
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: Lutrol

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw

Doses:

1000, 3100 and 5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Animals were periodically observed for clinical signs on the treatment day and twice daily thereafter until the end of the observation period. Body weights were recorded right before application and weekly thereafter.
- Necropsy of survivors performed: yes, on a random basis
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 100 mg/kg bw

Based on:

test mat.

Remarks on result:

other: based on the death of 4/10 animals each in the 3100 and 5000 mg/kg bw group

Mortality:

No mortality occurred in the 1000 mg/kg bw group. In the 3100 mg/kg bw group, 1/5 males and 3/5 females died during the first 8 h after application of the test substance. In the 5000 mg/kg bw group, 1/5 males and 3/5 females were found dead during the first hour after application of the test substance.

Clinical signs:

other: No clinical signs were observed in the 1000 mg/kg bw group. In the 3100 and 5000 mg/kg bw groups, the general condition of all animals was decreased and they layed down in side or prone position and showed signs of sedation and anaesthesia. These symptoms

Gross pathology:

Necropsy of surviving animals on a radom basis revealed no substance-related findings. No necropsy or histopahological examination was done in the animals that died during the observation period.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 100 mg/kg bw

Quality of whole database:

The available information comprises adequate, reliable and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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

The acute toxicity of ethylparaben was assessed in several oral toxicity studies.

 

In the key study, acute oral toxicity was investigated according to OECD 401 (Loeser, 1982). Three groups of 5 male and 5 female Wistar rats were treated with ethylparaben in doses of 1000, 3100 and 5000 mg/kg bw by oral gavage. No mortality occurred in the group dosed with 1000 mg/kg bw. In the group treated with 3100 mg/kg bw, 1/5 males and 3/5 females died during the first 8 h post-dose. In the 5000 mg/kg bw group, 1/5 males and 3/5 females were found dead during the first hour after application of the test substance.

No clinical signs were observed in any animal of the 1000 mg/kg bw group during the 14 d observation period. In all males and females of the 3100 and 5000 mg/kg bw groups, decreased general condition was noticed and they showed signs of sedation and anaestesia and layed down in side or prone position during the first 24 to 48 h after treatment. Until the end of the 14 d observation period, no other clinical signs were observed in any animal of the high dose group. Necropsy of the surviving animals on a random basis did not reveal any abnormalities.

The LD50 is > 3100 mg/kg bw for male and female rats.

 

In a further acute oral toxicity study performed equivalent to OECD 401, five female albino rats per dose group were treated with 2150 and 4640 mg/kg bw of the test substance in propylene glycol by oral gavage (Anonymous, 1980). All animals survived in the 2150 mg/kg bw group, whereas 3/5 animals died in the 4640 mg/kg bw group within the observation period of 7 days. All surviving animals appeared normal throughout the study period. No substance-related findings were observed at necropsy.

The LD50 was considered to be 4300 mg/kg bw for female rats.

Justification for selection of acute toxicity – oral endpoint
The selected study is the most adequate and reliable study with the lowest dose descriptor.

Justification for classification or non-classification

The available data on the acute oral toxicity of the test substance does not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and is therefore conclusive but not sufficient for classification.