Registration Dossier

Administrative data

Description of key information

An unpublished study reports a guinea pig maximization test according to Magnusson and Kligman method. MEG was concluded to have low potential to produce delayed contact hypersensitivity (Bio/dynamics, Inc., 1990; study owner: The Dow Chemical Company).
Kurihara et al. (1996) reported a guinea pig maximization test. Female guinea pigs were given ethylene glycol (diluted in olive oil). No skin sensitization properties were found.
Kurihara et al. (1996) also reported a human patch test. The very faint erythema caused by the substance was judged to be negative concerning sensitization.
A controlled repeated insult patch test (RIPT) in 401 male and female subjects concluded that MEG has low potential to induce dermal sensitization in human subjects (TKL Research, Inc., 1988; study owner: The Dow Chemical Company).
A BASF (1991) guinea pig maximisation test conducted with diethylene glycol (CAS 111-46-6) according to EU Method B.6 did not lead to skin reactions.
An OECD SIDS document for triethylene glycol (CAS 112-27-6) is available covering a repeated insult patch test with human participants. The test showed no sensitizing properties of the test substance.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
according to Magnusson and Kligman
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was conducted in 1996 when the GPMT was an international accepted and recommended method to assess skin sensitizing properties.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Housing: individually, in stainless-steel wire-mesh cages

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2°C
- Humidity (%): 55 ± 5%
Route:
intradermal and epicutaneous
Vehicle:
olive oil
Concentration / amount:
0.2 % (w/w) and 100 %
Route:
epicutaneous, occlusive
Vehicle:
olive oil
Concentration / amount:
100 %
No. of animals per dose:
4
Details on study design:
This test was performed according to the method of Magnusson and Kligman. A total of 19 guinea pigs were used. For sensitization, the solution for injection was prepared by mixing equal volumes of Freund's complete adjuvant and distilled water using two 5-mL glass syringes and stainless-steel syringe connector. The experimental dentin primers were diluted with olive oil and acetone (7: 3 v/v). Based on the findings of one of our previous papers, the 2-HEMA, HD and EG solutions for this test were diluted with olive oil and acetone at concentrations of 0.2% by weight. In the first stage of induction, 50 µL of each experimental dentin primer solution was intradermally injected into the back skin near the neck. One week later, as the second stage of induction, a filter paper patch soaked in 0.2 mL (100%) of experimental dentin primer was placed onto the shaved back of the guinea pigs. Finally, the experimental dentin primers (100 µL and 100% each) were applied to the skin at two sites using an Eppendorf filter paper under a sealed dressing for induction for 24 hours.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100 µL
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
none
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In an unpublished study according to Magnusson and Kligman method, Hartley Albino guinea pigs were intradermally injected with 5% MEG alone or in combination with Freund's Complete Adjuvant (FCA). 10 male and 10 female test animals were subsequently exposed to a total of nine 48-hour induction patches with undiluted MEG in combination with SLS to cause mild irritation at the site of application. 10 naïve animals (5 males and 5 females) were concurrently included to test for non-specific irritation to the test substance. On Day 21, all animals were exposed to topical challenge with 100% MEG and the dermal responses were evaluated at 24 and 48 hours post application. All animals challenged with MEG exhibited no (zero) dermal responses to the non-irritating test substance concentration: readings of 0 in 20/20 test animals and 10/10 naïve control animals. Under conditions of this GPMT study MEG was concluded to have low potential to produce delayed contact hypersensitivity (Bio/dynamics, Inc., 1990; study owner: The Dow Chemical Company). 

Kurihara et al., (1996) reported a guinea pig maximization test with female animals. The test substance had been diluted in olive oil. None of the four animals tested showed any positive reaction.

The same publication also reported a human patch test with 62.5 wt% ethylene glycol that has been judged negative. The very faint erythema caused by the substance was judged to be negative concerning sensitization according to the criteria given by ICDRG (International Contact Dermatitis Research Group). The authors concluded that the defatting properties of EG are likely to be responsible for the slight irritation.

The result of this published study is supported by the outcome of the controlled repeated insult patch test (RIPT) in four hundred and one (401) male and female subjects 18 years or older (TKL Research, Inc., 1988; study owner: The Dow Chemical Company). MEG was tested under 24 hour occlusive and semi-occlusive patches applied to the infrascapular skin, nine times during the induction period, with the sites being evaluated after additional 24 hours for local irritancy. Erythema was seen in small proportion of subjects during induction period suggestive of cumulative irritation and fatigue reactions. Induction period was followed by the rest period and sensitization potential was assessed with the 24 hour patch challenge at distal sites during 6thweek of the test. Three subjects exhibited skin reactions from challenge application with MEG that were not confirmed after re-challenge and were judged to be irritant reactions to MEG, as their reactions were similar or lesser compared to the skin responses observed during induction period and the skin reactions did not get greater over time after challenge or re-challenge MEG application. Therefore, MEG is concluded to have low potential to induce dermal sensitization in human subjects. 

Additionally, a QSAR estimation has been operated for ethylene glycol. The test substance was well within the overall applicability domain of the system. The corresponding QMRF and QPRF files have been added to the dossier for a detailed description of the applied QSAR model and to reflect the OECD principles for the validity of the model.

To further support these results, read-across to diethylene glycol (CAS 111-46-6) has been performed:

BASF (1991) reported a guinea pig maximisation test conducted according to EU Method B.6. For intradermal induction a 5% diethylene glycol (DEG) formulation in NaCl and for epidermal induction a 75% DEG formulation in water were used. A 50% DEG formulation in water was applied for challenge. No skin reactions could be observed.

Additionally, an OECD SIDS document for triethylene glycol (CAS 112-27-6) is available covering a repeated insult patch test with human participants (37 males and 360 females, age 18-85). Occlusive or semiocclusive patches were applied to the infrascapular area of the back of the paricipants, either to the right or left of the midline. Subjects removed patches at 24 hrs, and new patches were applied at 48 hrs. Induction phase consistent of 9 consecutive applications of 0.2 ml test material. After a two-week rest phase, the challenge phase was initiated. Subjects removed patches 24 hrs after application and sites were graded at 48 and 72 hrs after application. This repeated insult patch test showed no sensitizing properties of triethylene glycol.

For a justification of the read-across please refer to Chapter 13 “assessment reports”. A detailed justification is given there. Additional information concerning the endpoint skin sensitization can be found in the TPRF file attached.

The read-across strategy concerning the endpoint skin sensitization is further supported by a negative sensitization prediction of the OECD Toolbox (version 3.2) using data on structural analogs as well as information obtained from the chemical structure and physico-chemical parameters of the substance of interest. See “attached documents” for the corresponding TPRF (QSAR Tool Box Prediciton Report), further explaining the prediction and its underlying assumptions.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified as skin sensitizer under Regulation (EC) No 1272/2008, as amended for the eighth time in Regulation (EU) No 2016/218.