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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981-10-20 to 1981-11-17
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: HLD protocol number P 1/152 and recommend guidelines of the USA Interagency Regulatory Liaison Group (IRLG) Testing Standards and Guidelines Work Group (January 1981)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Nonylphenol
EC Number:
246-672-0
EC Name:
Nonylphenol
Cas Number:
25154-52-3
IUPAC Name:
2-nonylphenol
Constituent 2
Chemical structure
Reference substance name:
Phenol, 4-nonyl-, branched
EC Number:
284-325-5
EC Name:
Phenol, 4-nonyl-, branched
Cas Number:
84852-15-3
Molecular formula:
C15H24O
IUPAC Name:
4-(7-methyloctyl)phenol
Details on test material:
- Name of test material (as cited in study report): Nonylphenol
- Substance type: pure active substance
- Physical state: liquid
- Storage condition of test material: in the dark at room temperature
- Other: Date of manufacture: 1981-10-12

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: 35 days
- Weight at study initiation: male = 145 - 165 g; female = 150 - 165 g
- Fasting period before study: overnight before application
- Housing: in solied-bottomed polypropylene boxes containing softwood sawdust bedding
- Diet (e.g. ad libitum): R4 Complete feed for rats ad libitum, supplied by Ssniff Spezialfutter GmbH, Soest, Germany
- Water (e.g. ad libitum): mains water ad libitum (limited analyses of the mains water at twice yearly intervals)
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23
- Humidity (%): 40 - 70
- Air changes (per h): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
paraffin oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
10 mL/kg bw
Doses:
Main test: 800, 1040, 1352, 1758 mg/kg bw
Range-finding test: 1400, 1700. 2000, 2300, 2600 mg/kg bw
No. of animals per sex per dose:
Main test: 5
Range-finding test: 2
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (7 days in the dose range finding study)
- Frequency of observations and weighing: Examination of clinical signs 15 min, 30 min, 1, 2 and 4 h after the treatment and daily observations thereafter; bodyweights were determined on the day before treatment, on the day of treatment and on days 7 and 14 after treatment. (Dose range finding study: daily observations for mortality, body weight were recorded on the day of treatment)
- Necropsy of survivors performed: yes (not in the dose range finding study)
- Other examinations performed: no
Statistics:
Probit method (95% confidence limit); Finney, D.J. 1964, Statistical methods for biological assay, 2nd edition, London, Charles Griffin

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 412 mg/kg bw
95% CL:
>= 1 210 - <= 1 647
Sex:
male
Dose descriptor:
LD50
Effect level:
1 246 mg/kg bw
95% CL:
>= 1 054 - <= 1 472
Sex:
female
Dose descriptor:
LD50
Effect level:
1 648 mg/kg bw
95% CL:
>= 1 196 - <= 2 269
Mortality:
- Number of deaths at each dose: Range-finding: 1400, 2000 mg/kg: 3/4 animals; 1700, 2300, 2600 mg/kg: 4/4 animals, time of deaths not recorded
Main test:
800 mg/kg: 0/5 male animals, 0/5 female animals
1040 mg/kg: 2/5 male animals (deaths on day 3), 1/5 female animals (death on day 2)
1352 mg/kg: 2/5 male animals (deaths on days 2 and 3), 1/5 female animals (death on day 3)
1758 mg/kg: 5/5 male animals (4 males found dead on day 3, the remaining male found dead on day 4), 3/5 female animals (1 female found dead on day 2, 2 on day 3)
Clinical signs:
800 mg/kg: 15 min after dosing excessive salivation, pushing of the bedding with the nose was noted. From 30 minutes after dosing, lethargy and half of fully closed eyes were observed (in one animal up to day 2). Other isolated clinicals signs included slow shallow breathing, hunched posture, nasal haemorrhage, loose faeces or brown staining of the fur in the anal region and yellow staining of the fur in the ano-genital region. All animals appeared normal by day 3 of the observation period (except one animal which showed noisy difficult breathing on day 8).
1040 mg/kg: Prior to death the animals appeared lethargic, hunched posture and/or half closed eyes were noted, 2 animals showed hypothermia. The surviving animals ahowed similar clinical signs to those treated with 800 mg/kg but the incidence of lethargy was greater. In addition prostration was noted in 2 animals one hour after dosing. All surviving animals appeared normal by day 4.
1352 mg/kg: A greater incidence of excessive salivation, lethargy, hunched posture, closing of eyes and passage of liquid faeces was noted than at lower dose levels. All surviving animals appeared normal by day 4.
1758 mg/kg: Prior to death all animals were either lethargic or prostrate and slow shallow breathing, hunched posture, closed eyes and hypothermia were observed in the majority of these animals. The 2 surviving animals were lethargic on days 2 and 3 but appeared normal from day 4 onwards.
Body weight:
All animals showed normal changes in body weight.
Gross pathology:
Reddening, haemorrhage and erosion of the mucosal surface of the stomach were observed in a proportion of the animals that died during the observation period. Moderate congestion of the right lung lobes and the presence of large amounts of gas in the gastro intestinal tract were observed in one female given 1758 mg/kg that died.
With the exception of one animal, all surviving animals showed varying degrees of raised white thickening of the mucosal surface of the cardiac region of the stomach

Any other information on results incl. tables

Table #: Number of animals dead, and with evident toxicity, and time range within which mortality occurred

 

Dose
(mg/kg bw)

Mortality (# dead/total)

Time range of deaths (day(days)

Male

Female

Combined

800

0 / 5

0 / 5

0 / 10

-

1040 2 / 5 1 / 5 3 / 10 2 - 3
1352 2 / 5 1 / 5 3 / 10 2 - 3
1758 5 / 5 3 / 5 8 / 10 2 - 4

 

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Toxicity Category IV Criteria used for interpretation of results: EU
Conclusions:
Nonylphenol is of acute oral toxicity category 4 based on LD50 (rat) according Regulation (EC) No 1272/2008.
Executive summary:

In an acute oral toxicity study, groups (5/sex) of Sprague Dawley rats were given a single oral dose of 98% (w/w) Nonylphenol in liquid paraffin at doses of 1400, 1700, 2000, 2300 or 2600 mg/kg bw. Animals were then observed for 14 days.

 

Oral LD50 Males = 1246 mg/kg bw (1054 - 1472)

      Females = 1648 mg/kg bw (1196 - 2269)

      Combined = 1412 mg/kg bw (1210 - 1647)

Isononylphenol is of acute oral toxicity (category 4) based on the LD50 in male rats. 

This acute oral study is classified as acceptable. It is comparable to guideline study with acceptable restrictions.