Registration Dossier

Administrative data

Description of key information

The submission substance was found to be non-toxic or harmful by the oral route of exposure study conducted according to OECD Guidelne 401 and EC guideline B1. 
The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight. The substance is not classified as toxic or harmful by the dermal route of exposure.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Dose volume of 20 ml/kg bw used to administer dosage of 2000 mg/kg bw. Dose volume should not normally exceed 10 ml/kg for aqueous vehicles. Does not affect relevance of results produced.
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
yes
Remarks:
Dose volume of 20 ml/kg bw used to administer dosage of 2000 mg/kg bw. Dose volume should not normally exceed 10 ml/kg for aqueous vehicles. Does not affect relevance of results produced.
GLP compliance:
yes (incl. certificate)
Remarks:
Date of inspection: May and June 2000. Date of signature: 2nd August 2000
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sandhofer Weg 7, D-97633, Sulzfeld
- Age at study initiation: Males - 36 days, Females - 45 days
- Weight at study initiation: 164 to 210 g
- Fasting period before study: 16 hours
- Housing: Granulated textured wood was used as bedding material for the cages. During the 14-day observation period animals were kept in groups of 2 or 3 animals in MARKOLON cages (type III).
- Diet: ad libitum access
- Water: as libitum access to tap water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C (+/- 3°C)
- Humidity (%): 50% (+/- 15%)
- Air changes (per hr): Not stated in report
- Photoperiod (hrs dark / hrs light): The rooms were lit (150 lux at approximately 1.5 m room height) and darkened for periods of 12 hours each.

IN-LIFE DATES: From: Day 0 To: Day 14 (Day of sacrifice)
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2000 mg/ 20 ml/kg bw
- Amount of vehicle (if gavage): 20 ml/kg bw
- Justification for choice of vehicle: not stated in report
- Lot/batch no. (if required): not stated in report
- Purity: not stated in report

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg

DOSAGE PREPARATION (if unusual): not applicable

CLASS METHOD (if applicable)
- not applicable
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Observations were performed before and immediately, 5, 15, 30 and 60 minutes, as well as 3, 6 and 24 hours after administration. All surviving animals were observed daily for a period of 14 days.

- Necropsy of survivors performed: yes. Gross pathological changes were recorded.

- Other examinations performed: during the follow-up period, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and smotomotor activity, behavious pattern. Attention paid to possible tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma. bodyweight.
Statistics:
Standard deviation
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality observed.
Clinical signs:
No substance-related findings.


Body weight:
No inhibition of bodyweight gain
Gross pathology:
No substance-related findings
Other findings:
- Not detailed in report
Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The substance is not classified as toxic or harmful by the oral route of exposure.
Executive summary:

A study to determine the oral toxicity of the test substance was conducted following the OECD Guidelne 401 and EC guideline B1.

Under the test conditions (a single oral dose of the test material at 2000 mg/kg bw) to rats revealed no toxic symptoms.

The substance is not classified as toxic or harmful by the oral route of exposure.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 1-2) and consistent studies, 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

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 23 March 2010 and 06 April 2010.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Date of Inspection: 15 Septemeber 2009 Date of Signature: 26 November 2009
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Test Animals:
Animals: Rat, HsdRccHan: WIST

Rationale: Recognized by international guidelines as a recommended test system.

Breeder: Harlan Laboratories UK Limited, Bicester, Oxon, UK.

Number of Animals per Group: 5 males and 5 females

Total number of Animals: 5 males and 5 females

Age when treated: At the start of the study the animals weighed at least 200g, and were eight to twelve weeks of age. The weight variation did not exceed ± 20% of the mean weight for each sex.

Identification: After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card.

Acclimatization: At least 5 days under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

Environmental Conditions:
Conditions:
The temperature and relative humidity were within the range of 19 to 25 °C and 30 to 70 % respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Accommodation:
The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.

Diet:
Free access food (2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study. The diet was routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.

Water:
Free access to mains drinking water was allowed throughout the study. The drinking
water was routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
Type of coverage:
semiocclusive
Vehicle:
arachis oil
Details on dermal exposure:
One day before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10 % of the total body surface.

Using available information on the toxicity of the test material, a single group of animals was treated as follows:

Dose Level Number of Rats
(mg/kg) Male Female
2000 5 5

The animals were caged individually for the 24 hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.

A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self adhesive bandage. The animals were caged individually for the 24 hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.

After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material. The animals were returned to group housing for the remainder of the study period.

The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
Duration of exposure:
24 hours
Doses:
2000 mg /kg body weight
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and
scored according to the following scale from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the
Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31:

EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation Value

No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to slight eschar formation (injuries in depth) 4

Oedema Formation

No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4

Any other skin reactions, if present were also recorded.

Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.

At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external
examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were
retained.

Rationale: The dermal route was selected as the most appropriate route of exposure and the results of the study are believed to be of value in predicting the likely toxicity of the test material to man.




Statistics:
Example: No statistical analysis was performed.
Preliminary study:
Not described.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 95% confidence limits not reported.
Mortality:
No deaths occurred during the study.


Clinical signs:
No clinical signs were observed during the course of the study.

There were no signs of dermal irritation.
Body weight:
Animals showed expected gains in bodyweight over the study period except for one female which showed no gain in bodyweight during the first week with expected gain in bodyweight during the second week.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
None.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.
Executive summary:
IntroductionThe study was performed to assess the acute dermal toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following:

§        OECD Guidelines for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted 24 February 1987)

§        Method B3 Acute Toxicity (Dermal) of CommissionRegulation (EC) No. 440/2008

Method. A group of ten animals (five males and five females) was given a single, 24‑hour, semi‑occluded dermal application of the test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Dermal Irritation. There were no signs of dermal irritation.

Bodyweight. Animals showed expected gains in bodyweight over the study period except for one female which showed no gain in bodyweight during the first week with expected gain in bodyweight during the second week.

Necropsy. No abnormalities were noted at necropsy.

Conclusion. The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.6, of Regulation (EC) No 1907/2006.

Additional information

Acute Oral toxicity: A study to determine the oral toxicity of the test substance was conducted following the OECD Guidelne 401 and EC guideline B1. Under the test conditions (a single oral dose of the test material at 2000 mg/kg bw) to rats revealed no toxic symptoms. The substance is not classified as toxic or harmful by the oral route of exposure.

Acute Dermal toxicity.The study was performed to assess the acute dermal toxicity of the test material in the Wistar strain rat. The method was designed to meet the OECD Guidelines and the Method B3 Acute Toxicity (Dermal) of CommissionRegulation (EC) No. 440/2008

The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

The substance is not classified as toxic or harmful by the dermal route of exposure.

Acute inhalation toxicity. Studies to determine the inhalation toxicity of the submission substance due to the inhalation route is deemed inappropriate as exposure to humans via inhalation is unlikely to occur. As the substance is a waxy solid, there is no potential for inhalable particles. Lanolin alcohols has a vapour pressure of 360 Pa at 20 °C. However, the vapour pressure was deemed to be quite high for a solid, and it was suspected that the sample contained water hence the magnitude of the results. EPI suiteTM (version 4.11) calculated vapour pressure results in <0.001 Pa (at 25°C). In addition the boiling temperature of the test material has been determined to be 220 °C - 420 °C at normal pressure indicating that Lanolin alcohols is not highly volatile. Furthermore, there are no spray applications of Lanolin alcohols.

Therefore, under normal use and handling conditions, inhalation exposure and thus availability for respiratory absorption of the substance in the form of vapours, gases, or mists is not significant.

In conclusion, Lanolin alcohol is marketed in a non-granular form and is not used in spray applications. Therefore, exposure by inhalation is unlikely to occur and no acute toxicity inhalation test was performed due to animals welfare reasons.


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 selection of acute toxicity – dermal endpoint
The reliable GLP compliant OECD Guideline study was chosen.

Justification for classification or non-classification

The submission substance was found to be non-toxic or harmful by the oral route of exposure study conducted according to OECD Guidelne 401 and EC guideline B1.

The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

The substance is not classified as toxic or harmful by the dermal route of exposure.