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Description of key information

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:
other: no information on GLP
Qualifier:
no guideline followed
Principles of method if other than guideline:
According to Magnusson Kligman Assay
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Intradermal induction 5%, Epicutaneous induction 10%, Epicutaneous challenge 10%
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Intradermal induction 5%, Epicutaneous induction 10%, Epicutaneous challenge 10%
No. of animals per dose:
10 male and 10 female
Challenge controls:
Irritation control animals, five male and five female guinea pigs, received the same challenge procedures as in the definitive sensitization study, but did not have preceding intradermal and/or epicutaneous induction procedures
Details on study design:
Groups of 10 male and 10 female guinea pigs each received 0.1 ml intradermal induction injections into 2 sites each of the clipped shoulder skin as follows: 50% (v/v) Freund's complete adjuvant (FCA) water emulsion, the test material or vehicle, and the test material in FCA/water emulsion or FCA/water emulsion. Epicutaneous inductions were conducted 7 days later. The test material was applied to a 2 x 4 cm filter paper, which was then placed on the test site and secured with tape. The patches were left in place for 48 h, after which they were removed and the skin wiped free of any excess test material.
Epicutaneous challenge was undertaken by applying 2 x 2 cm filter paper squares soaked in the ethylenediamine solution to a previously untreated site (right flank) 14 days after epicutaneous induction (i.e., 21 days from the start of the study). Patches were left in place for 24 h, and the sites inspected for signs of irritation 24-48 h after removal of the occlusive dressings.

Skin responses were evaluated and scored. 45% of animals tested showed signs of sensitisation.

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Ethylenediamine is sensitising.
Executive summary:

In a Guinea Pig Maximisation test ethylene diamine was a sensitiser. Cross sensitisation with other ethylene amine substances was observed.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Based on the available Guinea Pig Maximisation study, with an intradermal induction of 5%, and based on moderate effects in humans a category of 1B is justified.


Migrated from Short description of key information:
Ethylenediamine is shown to be sensitising to Guinea Pigs. In a GPMT study the intradermal injection dose was 5%.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

In 1999 the World Health Organization published their Concise International Chemical assessment Document 15 on 1,2 –Diaminoethane (ethylenediamine).  This document referenced several case reports of respiratory senitisation apparently due to exposure to ethylene daimine but the incidence was not specified other than in one report when it was quoted to be 10%.  This was a retrospective study so no challenge tests were done.   Aldrich, FD, Strange AW and Geesman RE published in 1987 Smoking and ethylenediamine sensization in an industrial population, J. Occup Med 1987 Apr; 29(4) 311-314., from the abstract the incidence they was 38 out of 337 workers ca. 11%.

 

The paper by Lars Hagmar, MD et.al, Piperazine induced Occupational Asthma, Journal of occupational Medicine, Vol 24 No 3. March 1982, mention 2 individuals sensitized in a population of 130 workers, who had been exposed to ethylenediamine which was used until the previous year i.e. ca, 3% incidence.

 

In a large review paper authored by M. Chan-Yeung and J-L. Malo, Aetiological agents in occupational asthma in the Eur Resp J 194, 7 , 346-371, they reviewed about 200 agents implicated in occupational asthma.  While they only included some case reports for ethylene diamine they did give percentage incidence values for some known strong respiratory sensitisers such as the diisocyanates, including TDI and HDI and some anhydrides.  For these the percentage incidences were in the order of 28-35%.  As we would expect these substances to be classified as 1A for respiratory sensitization we see this level of incidence being necessary to support a conclusion of high frequency. Based on this we would interpret the incidence of ca. 3-11% seen with ethylene diamine as being in the low to moderate frequency range and therefore supporting a classification of 1B.  None of the admittedly limited available information supports a conclusion of 1A.

 

So we recommend that ethylenediamine be classified as 1B for respiratory sernsitisation based on the above information.


Migrated from Short description of key information:
Based on data from exposed workers, ethylene diamine can be considered a respiratory sensitiser.

Justification for classification or non-classification

Ethylene diamine is classified as a skin and respiratory sensitiser.