Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion
Remarks:
other: human patch testing
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004
Reliability:
1 (reliable without restriction)
Qualifier:
no guideline followed
Principles of method if other than guideline:
To determine by epidermal contact the primary irritation potential of the test material, ColaMoist.
53 subjects, male and female age range 16 - 77 years were selected for this evaluation. 52 out of the 53 completed the study. The remaining person discontinued for personal reasons unrelated to the study.
Participants had to be over 16 and have no visible skin disease or skin complaint which might be confused with a reaction.
They were prohibited to use topical or systemic steroids and/or antihistamines for at least 7 days prior to the study initiation.
Completion of a medical history form and a consent form were required.
Exclusion criteria included; ill health, taking medication, pregnancy or nursing, a history of adverse reactions with cosmetics or personal care products.
GLP compliance:
no
Species:
human
Strain:
other: male and females age range 16 - 77 years
Type of coverage:
occlusive
Preparation of test site:
other: no preparation noted. Cleanliness assumed.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.2 ml of the ColaMoist 70% active solution was applied to the 3/4 x 3/4 inch absorbent pad of an adhesive dressing. (The dressings were supplied by TruMed Technologies of Burnsville, MN, USA). The patch was applied to the upper back between the scapulae of each individual.
Duration of treatment / exposure:
The test material remained in contact with the skin for a total of 48 hours.
Observation period:
The site was observed after 48 hours following removal of the patch and then re-evaluated after 72 hours
Number of animals:
52 humans
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: No subject showed any visible skin reaction from the test after 48 hours and also after 72 hours
Other effects:
None.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Under the conditions of the test, ColaMoist 200 at 70% active solution did not indicate a potential for dermal irritation
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Recognised methodology used for testing in circumstances where animal testing is not permitted i.e. cosmetics. Testing carried out by a recognised test facility under GLP conditions by trained laboratory personnel. Test method B.48 / OECD 438 - Isolated Chicken Eye Test (ICE) Method is an in vitro test method that may be used to identify chemicals (substances or mixtures) as either 1) causing “serious eye damage” (CLP category 1), or 2) not requiring classification for eye irritation or serious eye damage according to the CLP. However, this test is only recommended to identify chemicals inducing serious eye damage, i.e. chemicals to be classified as CLP Category 1, without further testing, and also recommended to identify chemicals that do not require classification for eye irritation or serious eye damage • If the results of testing the substance is not classified as Cat 1 under CLP or not classified, more testing is required • May result in false positive predictions for alcohols and false negative predictions for solids and surfactants
Qualifier:
equivalent or similar to
Guideline:
EU method B.48 (Isolated chicken eye test method for identifying occular corrosives and severe irritants)
Deviations:
not specified
GLP compliance:
yes
Remarks:
Performed under Good Laboratory Practice principles (including govenunent regulations to the extent applicable) and in accordance with standard operating procedures and applicable standard protocols. Quality assessed.
Species:
other: hen's egg
Strain:
other: white leghorn
Details on test animals or tissues and environmental conditions:
Not applicable -no live animals used.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
5% active solution
Duration of treatment / exposure:
The test or.reference article, at a dosage of three-tenths of one milliliter (0.3 ml) of a liquid or three-tenths of one gram (0.3 g) of a solid was then administered to each of four (4) CAM's. Twenty seconds later, the test or control article was rinsed from each CAM with five (5) milliliters of physiological saline. All CAM's •were observed immediately prior to test article administration and at 30 seconds. two (2) and five (5) minutes after exposure to the test article. The reactions of the CAM, the blood vessels, including the capillaries, and the albumin were examined and scored for irritant effects.
The numerical, time dependent scores were totaled for each CAM. Each reaction type can be recorded only once for each CAM, therefore the maximum score per CAM is 32. The mean score was determined for all CAM's similarly tested.
Two reference materials were used as a comparison to the ColaMoist 200 (5% active aqueous sample).
These were (1) Johnson's baby shampoo and (2) Prell shampoo (no data on pH of this material). Both reference materials are commercially available shampoos that have a similar % active ingredient level to the ColaMoist 200 (5% active) material
Details on study design:
Fresh, fertile, White Leghorn eggs were obtained from Avian Services in Frenchtown, New Jersey. They were stored at this facility for up to seven (7) days, at 13° C, before being incubated. For incubation the eggs were placed, on their sides, in a Kuhl incubator. The incubator is such that the eggs are automatically rotated once every hour. The temperature was controlled at 99° F (± I 0 with a relative humidity of 60 - 70% for the ten (I0) days of incubation. On day eight (8) the eggs were turned so that the acutely angled end faced down.

On day ten ( I 0) each egg was removed from the incubator and placed in a Plexiglas work enclosure. This enclosure had been preheated and humidified so that its environment approached that of the incubator. A cut was made in the Iaeger end of each egg, where the air sack is located. A Dremel11 Moto-Flex Tool (model 232-5) equipped with a Dremel-,; Cut-Off Wheel (No. 409) was used to make each cut. Forceps were then used to remove the shell down to the shell­
membranc junction. The inner egg membrane was then hydrated with a warm, phyiological saline solution. The saline was removed after a two (2) to five (5) minute exposure. Utilizing pointed forceps, the inner egg membrane was then carefully removed to reveal the CAM.

The test or.reference article, at a dosage of three-tenths of one milliliter (0.3 ml) of a liquid or three-tenths of one gram (0.3 g) of a solid was then administered to each of four (4) CAM's. Twenty seconds later, the test or control article was rinsed from each CAM with five (5) milliliters of physiological saline. All CAM's •were observed immediately prior to test article administration and at 30 seconds. two (2) and five (5) minutes after exposure to the test article. The reactions of the CAM, the blood vessels, including the capillaries, and the albumin were examined and scored for irritant effects.
Irritation parameter:
overall irritation score
Remarks:
Mean CAM score
Basis:
mean
Score:
2.5
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
other: ColaMoist 200 (5% active) test sample
Irritation parameter:
overall irritation score
Remarks:
Mean CAM score
Basis:
mean
Score:
11
Max. score:
12
Reversibility:
other: not applicable
Remarks on result:
other: Johnson's baby Shampoo - Reference 1
Irritation parameter:
overall irritation score
Remarks:
Mean CAM score
Basis:
mean
Score:
24
Max. score:
26
Reversibility:
other: not applicable
Remarks on result:
other: Prell shampoo - Reference 2
Irritant / corrosive response data:
Each article was classified using the following scoring system
Irritation Potential - Practically None - Score 0 - 4.9
- Slight - Score 5.0 - 9.9
- Moderate - Score 10.0 - 14.9
- Severe - Score 15 - 32

Previous studies have shown that the CAM of the hen's egg is more sensitive to lquid irritants than is the rabbit eye. Therefore, 50% dilutions of the liquid test and reference articles were used.

Historical in-vivo testing on Johnson's reference product has shown this material to be 'moderatley irritating' eliciting scores approaching 10 at 24 hours when dosed at 100% and tested using the draize ocular irritation method.

The Prell reference product under the same in-vivo Draize testing has given scores approaching 30 at 24 hours when dosed at 100%.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The scores from the CAM test measured against known reference materials whose in-vivo eye irritation results are known show that ColaMoist 200 (5% active solution) has little or no irritant effect by the Hen's Egg in-vitro method.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin and Eye irritation tests available for Cola®Moist 200 have not been performed in-vivo on animals. Skin studies were made using humans (HRIPT type testing) and in-vitro hen’s egg testing performed for eye irritancy. The eye test was at low concentrations and compared against market available shampoos whose active ingredient was at a similar level (Johnson’s Baby and Prell US adult shampoo). The concentration used would not be considered valid for REACH testing.

However, in order to reduce the need for further testing on animals, evidence from testing already carried out on Cola®Moist 200 and also on a similar substance that can be considered as a suitable ‘read-across’ material, strongly suggests that this substance is not classified as irritating to eyes or skin.

Choline chloride (CAS 67-48-1) is a similar short chain quaternary amine of similar properties to Cola®Moist 200. This substance has been fully evaluated in an OECD report (SIDS Initial Assessment Report for SIAM 19, Oct 2004). Choline chloride has a widespread use as a food additive for animal husbandry since the early 1930s.and as such has been thoroughly tested for use in this area. The structure of Cola®Moist 200 is equivalent to a dimer of choline chloride joined through a OH-C-H linkage. Groupings are similar and therefore toxicological properties might be expected to be similar too although cannot be confirmed.

 

Skin Irritation - Studies in Animals

In an old, non-guideline, non-GLP, study with occlusive exposure, only minor skin irritation

(questionable reddening on the back of one rabbit) was found for a 70% aqueous formulation of the test substance. However, the degree of irritation would not be classifiable under GHS. In a non-guideline study for which the reliability could not be ascertained, no signs of skin irritation were observed.

Studies in Humans

In a 21-Day Cumulative Irritation study on 25 subjects with self-perceived sensitive skin

0.5 % choline chloride aqueous solution, a soap bar containing 5 % choline chloride and a liquid body soap containing 5 % choline chloride was evaluated compared to controls. The analysis of the cumulative irritancy demonstrated no significant differences between the samples containing choline chloride and their respective choline chloride free controls

Eye Irritation - Studies in Animals

In an old, non-GLP study, conducted broadly to OECD test guideline 405, only slight irritation was observed; however, the degree of irritation would not be classifiable under GHS. A 70% aqueous solution of the test substance was applied to one eye of one female and one male rabbit, the left eyes served as controls, to which saline was applied. After ten minutes, reddening of the eyes and tear secretion were observed. Slight reddening persisted up to three hours after application. No eye irritation or effects on the cornea were detectable after one day observation period. Post application readings were done after 1 and 3 hours, 1, and 8 days.

Conclusion

In rabbits, choline chloride may lead to a slight irritation of the skin and eye, which is, however, not sufficient to warrant a classification of choline chloride as an irritant under GHS.


Justification for selection of skin irritation / corrosion endpoint:
Only ColaMoist 200 (70% active) material test report available for consideration

Justification for selection of eye irritation endpoint:
Only ColaMoist 200 (5% active) material test report available for consideration

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Human, in-vitro and read-across data all suggest that this substance, ColaMoist 200, is not a skin and eye irritant and data is not sufficient to warrant classification under GHS.