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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Rationale for reliability of 2: data originates from an official review (European Comission and OECD SIDS); assessed to be valid to be used for risk assessment Rationale for grouping; the structural similarity is given by presence of butoxy ethylen glycol units; systemic exposure to 2-butoxyacetic acid as common mode of action for all members; comparable findings in repeated-dose toxicity for all members

Data source

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
Unnamed
Year:
2008
Reference Type:
review article or handbook
Title:
Unnamed
Year:
1997

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The study comprised induction, rest period and challenge. The induction consisted of repeated application of EGBE by patch and the rest period of 14 days. The challenge was then perfomred on the untreated site.
GLP compliance:
yes
Type of study:
patch test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

In vivo test system

Test animals

Species:
human

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
10% for induction and 10% challenge
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
10% for induction and 10% challenge
No. of animals per dose:
201 subjects
Details on study design:
Induction phase: 0.2 ml of 10% aqueous solution of EGBE applied under a patch for 24 hours to the backs of the subjects for a toal of 9 times over a 3 -week period.
Challenge phase: 10% EGBE applied to previously unexposed sites two weeks later

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
10%
No. with + reactions:
7
Total no. in group:
201
Clinical observations:
slight erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 7.0. Total no. in groups: 201.0. Clinical observations: slight erythema.
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
10%
No. with + reactions:
12
Total no. in group:
201
Clinical observations:
slight erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 10%. No with. + reactions: 12.0. Total no. in groups: 201.0. Clinical observations: slight erythema.

Any other information on results incl. tables

Study summary and result:

The sensitizing potential of 10% (v/v) EGBE in aqueous solution was assessed in human on 201 volunteers (TKL Research, 1992). Induction phase consisted in 9 consecutive application of EGBE. Patches were removed 24 h after application. Assessments of the sites of application were made at 48 h intervals and after new patches were reapplied. Following the ninth evaluation, the subjects were dismissed for a 14-day rest period. The challenge phase was initiated during the sixth week of the study, identical patches were applied to sites previously unexposed to EGBE. They were removed after 24 h of exposure.

7 of the 48h evaluations and 12 of the 72h evaluations showed slight erythema. One subject at the 72h reading had definite erythema. More severe responses which would have been expected if delayed contact sensitization had occurred were not observed. In conclusion, according to the authors, none of the 201 subjects completing the study showed evidence of sensitisation.

Category approach justification:

The skin sensitization potential of DEGDBE is to be assessed by read-across consideration. Three structurally related glycol ethers are identified as suitable surrogates. Together with DEGDBE, a category building is proposed to increase the robustness of the read-across consideration.

-Category members and chemical structures: the similarity in their structure is given by presence of butoxylated ethylene glycol at terminal position (Butyl-O-CH2-OH-).

Ethylene glycol butyl ether (EGBE)*

CAS 111-76-2

Butyl-O-CH2-OH

Diethylene glycol butyl ether (DEGBE)*

CAS 112-34-5

Butyl-O-CH2-O-CH2-OH

Diethylene glycol dibutyl ether (DEGDBE)**

CAS 112-73-2

Butyl-O- CH2-O-CH2-O-Butyl

Polyethylene glycol dibutyl ether (PolyEGDBE)***

CAS 31885-97-9

Butyl-O- CH2-O-CH2-O-CH2-O-Butyl

* EGBE and DEGBE are extensively investigated substances and reviews on their toxicity profiles are available in public domain (i.e. EU Risk Assessment Report, 2-Butoxyethanol (EGBE), CAS 111 -76 -2, 2008; Opinion on Diethylene Glycol Monobutyl Ether (DEGBE), SCCP/1043/06, 2006). **target chemical. ***Clariant own data, details provides in corresponding endpoint sutdy record.

 

-The proposed grouping is justified by the common mode of action, namely systemic exposure to 2-butoxyacetic acid (2-BAA) and/or butoxyethoxyacetic acid (BEAA):

- EGBE: 2-BAA is the major urinary metabolite (summarized in EU risk assessment, 2008)

- DEGBE: BEAA is the major urinary metabolite (Deisinger et al. 1989)

- DEGDBE: in 28-day study (Clariant own data) the urinary 2-BAA determination was incorporated; 750 mg/kg bw external dose level corresponded to 1400 mg/L 2-BAA in urine.

- PolyEGDBE: no experimental data is available; BEAA and/or 2-BAA as metabolite can be reasonably assumed due to the observed RBC reduction.

 

- The proposed grouping is justified by the comparable toxicity profiles, which reflects the toxicity action of 2-BAA and/or BEAA. Both metabolites are known to induce hemolysis (Udden 2002; Udden 2005).

- EGBE: hemolytic action demonstrated in acute and repeated dose toxicity studies (summarized in EU risk assessment, 2008)

- DEGBE: i.e. in 2 and 13 week oral toxicity studies (Johnson et al. 2005)

- DEGDBE: in 28-day study (Clariant own data) RBC reduction and hematuria was evident.

- PolyEGDBE: in dose-range finding study for OECD 422 (Clariant own data), RBC reduction was evident.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
EGBE is a non-sensitizer in human repeated insult patch test.
Executive summary:

The skin sensitization potential of DEGDBE was assessed based on the use of read-across. ethylene glcol butyl ether (EGBE) is considered to be one of the appropriate source chemical.

EGBE was a non-sensitizer in humen repeated insult patch test (10% induction and 10% challenge)

Likewise, the skin sensitization potential for DEGDBE is considered to be low.