Butanedioic acid, sulfo-, monoesters with lanolin alcs., disodium salts

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

other: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

From May 15th to June 25th, 2001

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Data have been obtained from a study on a substance with structural similarity. Good laboratory practice regulation GLP; United States Food and Drug Administration Good Laboratory Practice Regulation. Existing OECD TG 401 (EU B.1) data would normally be acceptable but testing using this deleted method must no longer be performed.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

The OECD 401 has been deleted in 2002. Now alternative is OECD Test Guidelines 423. Existing OECD TG 401 (EU B.1) data would normally be acceptable but testing using this deleted method must no longer be performed.

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

not specified

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Japanese Guidelines for Non-Clinical Studies of Drug Manual

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Lanoline Alcohol

IUPAC Name:

Lanoline Alcohol

Test material form:

other: solid

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 Deutschland GmbH
- Selection: according to EC and OECD guidelines;
- Numbers of animal: 1O (5 male, 5 female)
- Age at study initiation: male 36 days; female 45 days
- Weight at study initiation: 164 - 210 g
- Fasting period before study: discontinued approx. 16 hours before administration
- Housing: groups of 2 or 3 animals in Makrolon cages (type III), with bedding material in granulated texture wood; The cages where changed and cleaned twice a week. Periodic analysis of the bedding material for contaminants based on EPA/USA is conducted at least once a year by LUFA-ITL3.
- Diet : standard diet Altromin 1324. Periodic analysis of the food for contaminants based on EPA/USA is conducted at least twice a year by AUA2 (limitation for contaminants in the diet), with certificates of analysis.
- Water: tap water ad libitum. Drinking water is examined according to the 'Deutsche Trinkwasserverordnung, Bun- desgesetzblatt, Jahrgang 1990' by the Hamburger Wasserwerke, D-205 39 Hamburg, at least four times a year. In addition, drinking water samples taken at LPT are analysed by LUFA-ITL once a
year for means of bacteriological investigations according to the German 'Deutsche Trinkwasserverordnung, Bundesgesetzblatt, Jahrgang 1990, Anlage 4.
- Acclimation period: at least 5 adaptation days;
- Identification: by coloured marks and cage label.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 50% ± 15%
- Photoperiod (hrs dark / hrs light): 150 lux at approx 1.5 room height. Darkened for periods of 12 hours each.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

VEHICLE
- Selection of route of administration: according to OECD guidelines and most likely route of exposure.
- Administration volume: 20 ml/kg b.w

Doses:

2.000 mg/kg b.w

No. of animals per sex per dose:

5 males
5 females

Details on study design:

- Duration of the experiment: 1 test day, 2 recovery weeks.
- Duration of observation period following administration: 14 days
Observation at A 5, 15, 30, 60 minutes; 3, 6, 24 hours
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: yes

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Observations on mortality at least once daily.
No compound-related mortality. LD50 could not be calculated because no lethality occurred in the limit test.

Clinical signs:

other: No toxic symptoms

Gross pathology:

At the end of the experiments all surviving animals were sacrificed, dissected and inspected macroscopically.
All gross pathological changes were recorded. From animals which survive 24 hours or longer a microscopic examination of all organs which showed evident lesions was performed, if necessary.
Autopsy and macroscopic inspection of animals which died prematurely were carried out as soon as possible after exitus.

Other findings:

Observation at least once a day until each working day during the follow-up period: changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity, possible tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
 

Any other information on results incl. tables

Summarized results are indicated in Table 1.

Applicant's summary and conclusion

Interpretation of results:

other: not classified as harmful/toxic according to the CLP Regulation (EC) No.1272/2008

Conclusions:

Under the present test conditions a single oral administration 2000 mg (limit test) lanoline alcohol to rats revealed no toxic symptoms.
According to the EC-Commission directive 67/548/EEC and its subsequent amendments lanoline alcohol can be classified as relatively non-toxic.

Executive summary:

OECD Guideline 401 (Acute Oral Toxicity) has been performed in 2001.

The OECD 401 has been deleted in 2002. Now alternative is OECD Test Guidelines 423.

Five rats per sex were observed for 14 days following a single dose of 2000 mg/kg b.w (limit test).

Observations on mortality was done at least once daily, the LD50 could not be calculated due to no compound-related mortality observed.

Individual body weights were recorded before administration of the substance and at death changes in weight were calculated and recorded (table 1). Lanoline alcohol to rats revealed no toxic symptoms.

All gross pathological changes were recorded after autopsy and macroscopic inspection of animals.

Observations as changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity, possible tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma were observed.

No other findings were registered.

According to the EC-Commission directive 67/548/EEC and its subsequent amendments lanoline alcohol can be classified as relatively non-toxic.

Further testing may not be considered necessary.