Registration Dossier

Diss Factsheets

Administrative data

Description of key information

SKIN IRRITATION
Hydrocarbon waxes was determined to be not irritating according to two studies performed to GLP and the standardised guideline EPA OPPTS 870.2500 and another performed to GLP following the methodology set out in 40 CFR Part 798, EPA Health Effects Testing Guidelines - Subpart E - Specific Organ/Tissue Toxicity, September 1985.
EYE IRRITATION
Hydrocarbon waxes was determined to be irritating on a worst case basis. Three studies have been provided, all of which were conducted according to GLP where two followed standardised guidelines. Both Cerven, 2001 and 2002 were performed following EPA OPPTS 870.2400, whereas Moore (1993b) followed the methodology set out in 10 CFR Part 798, EPA Health Effects Testing Guidelines - Subpart E - Specific Organ/Tissue Toxicity, September 1985.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2nd February 2001 to 18th July 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP 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
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Sgarlat's Rabbitry , Harvey's Lake, PA on 20/12/00 and 17/01/00.
- Eyes were examined before selection and assignment to the study.
- Age at study initiation: Animals were born on 08/10/00 and 02/11/00.
- Weight at study initiation: 2.1 - 2.4 kg.
- Housing: Individually in suspended cages.
- Diet (e.g. ad libitum): Purina Rabbit Chow Diet #5321, provided daily.
- Water (e.g. ad libitum): ad libitum.
- Quarantine period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Controlled.
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle.
Vehicle:
unchanged (no vehicle)
Controls:
other: The contralateral eye served as a control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml.
- Concentration (if solution): Used as supplied.
Observation period (in vivo):
Up to 21 days post exposure at the following time points; 1, 24, 48 and 72 hours, including days 7, 14 and 21.
Number of animals or in vitro replicates:
Three in total, 1 male and 2 females.
Details on study design:
TEST PROCEDURE:
- One female animal was tested initially, then based on this reaction a further two were tested.
- The test material was placed into the conjunctival sac of one eye, formed by gently pulling the lower eyelid from the eye. The lids were held together for one second before the animal was released.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not performed.

OBSERVATIONS:
-Bodyweight, was recorded before the exposure.
- Any additional signs and the general health of the animals was recorded throughout the study.

SCORING SYSTEM: Draize scale (1977), which can be seen in table 1.

TOOL USED TO ASSESS SCORE:
- Sodium fluorescein dye was used at the following time points; 24, 48 and 72 hours and days 7, 14 and 21.
- Observations were made using a Mini-Maglit®.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 21 days in the female and 14 days in the male
Remarks on result:
other: Score of opacity
Irritation parameter:
iris score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 21 days in the female and 14 days in the male
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 21 days in the female and 14 days in the male
Remarks on result:
other: Score for redness
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: Mean of 24, 48 and 72 hours.
Score:
2.6
Max. score:
4
Reversibility:
fully reversible within: 21 days in the female and 14 days in the male
Irritant / corrosive response data:
Corneal opacity, noted in 3/3 eyes, cleared by day 21. Iritis, noted in 2/3 eyes, cleared by day 7.
Conjunctival irritation, noted in 3/3 days, cleared by day 21.
Other effects:
An instance of diarrhoea was the only abnormal physical sign noted during the study.

One animal was sacrificed on day 11 due to an injury not concurrent with treatment, the animal was replaced. None of the results from the sacrificed animal have been used in the study. This replacement is not thought to have affected the results of the study.

Table 2. Ocular Response

Animal No. and Sex Tissue Reading 1 hr 24 hrs 48 hrs 72 hrs day 7 day 14 day 21
Female 1 Cornea Opacity 0 0 2 0 0 0 0
  Area 0 0 1 0 0 0 0
SubTotal   0 0 10 0 0 0 0
Iris   0 0 0 0 0 0 0
SubTotal   0 0 0 0 0 0 0
Conjunctiva Redness 2 2 2 2 1 1 0
  Chemosis 3 3 3 2 2 0 0
  Discharge 2 2 2 2 1 0 0
SubTotal   14 14 14 12 8 2 0
Total   14 14 24 12 8 2 0
Male 1 Cornea Opacity 0 2 2 2 0 0  
  Area 0 1 1 1 0 0  
SubTotal   0 10 10 10 0 0  
Iris   1 0 0 0 0 0  
SubTotal   5 0 0 0 0 0  
Conjunctiva Redness 2 2 2 2 1 0  
  Chemosis 3 3 2 2 0 0  
  Discharge 2 2 2 1 0 0  
SubTotal   14 14 12 10 2 0  
Total   19 24 22 20 2 0  
Female 2 Cornea Opacity 0 0 2 2 2 2 0
  Area 0 0 2 2 2 1 0
SubTotal   0 0 20 20 20 10 0
Iris   0 1 1 1 0 0 0
SubTotal   0 5 5 5 0 0 0
Conjunctiva Redness 2 2 2 2 2 0 0
  Chemosis 3 3 3 3 2 0 0
  Discharge 2 2 2 1 0 0 0
SubTotal   14 12 14 12 8 0 0
  Total   14 19 39 37 28 10 0
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the test material was determined to be an eye irritant. Three out of three animals scored ≥ 2 for conjunctival redness and chemosis, which were observed to be fully reversible within 21 days. The material tested in this study has a TAN range of 112-128 and is classified as Eye Irritation Category 2 according to EU CLP Regulation No. 1272/2008.
Executive summary:

In a GLP compliant eye irritation study, the ocular reaction caused by exposure to the test material was determined according to EPA OPPTS 870.2400. Three rabbits were exposed to the unchanged test material and observed over a 21 day period. Three out of three animals scored ≥ 2 for conjunctival redness and chemosis, which were observed to be fully reversible within 21 days. The material tested in this study has a TAN range of 112-128 and based upon these results is classified as Eye Irritation Category 2 according to EU CLP Regulation No. 1272/2008. Corneal opacity and iritis were also observed in the test animals; however these symptoms were not severe enough to contribute to the classification.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

SKIN IRRITATION

Three GLP compliant studies have been provided which all support the claim that the test material is not irritating.

Both Hoff (2001) and Hoff (2002) were performed according to GLP and the standardised guideline EPA OPPTS 870.2500, with a sufficient level of detail to assess the accuracy and reliability of the data. Both studies have been assigned a reliability score of 1 using the principles for assessing data quality as set out in Klimisch (1997). According to Regulation (EC) 1272/2008 the observed dermal reaction, seen in both studies, is not severe enough to trigger a classification and accordingly the results have been interpreted as “not classified”.

Moore (1993) was performed according to GLP and following a similar protocol to that set out in 40 CFR Part 798, EPA Health Effects Testing Guidelines - Subpart E - Specific Organ/Tissue Toxicity, September 1985. This study has been assigned a reliability score of 2 according to Klimisch (1997). The study reports the PDII to be 0.0, a result consistent with the other two studies in the conclusion that the test material is not irritating.

EYE IRRITATION

Three reliable studies are available for this endpoint. Cerven (2001) has been selected as the key study on a worst case basis for this substance with a TAN value of >40, where the test material has been determined to be a mild irritant.

 

Both Cerven (2001) and Cerven (2002) are GLP compliant studies which were performed to the standardised guideline EPA OPPTS 870.2400, with a sufficient level of detail to assess the accuracy and reliability of the data. Both studies have been assigned a reliability score of 1 using the principles for assessing data quality as set out in Klimisch (1997).

 

Moore (1993) is a GLP compliant with a sufficient level of detail regarding the methodology adopted to assess the accuracy and reliability of the data. The study has been assigned a reliability score of 2 using the principles for assessing data quality as set out in Klimisch (1997).


Effects on eye irritation: irritating

Justification for classification or non-classification

SKIN IRRITATION

The skin irritation studies indicate that the test material has no effect in skin irritation which requires the substance to be classified. Therefore the test material does not require classification in line with Regulation (EC) 1272/2008.

EYE IRRITATION

Hydrocarbon waxes (petroleum), oxidized is a complex combination of organic compounds obtained by air oxidation. The oxidation process is carried out under conditions of high temperature and pressure which can be varied to control the total acid number (TAN). The level of eye irritation varies based on the TAN. Hydrocarbon waxes (petroleum), oxidized with an acid number (TAN) ≤ 40 are not classifiable according to EU CLP Regulation No. 1272/2008 and with an acid number (TAN) > 40 are classified as Eye Irritation Category 2 according to EU CLP Regulation No. 1272/2008.