Butyl ethyl ether

Skin sensitisation

Administrative data

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: Study described in the present publication is comparable to guideline study OECD 406 (Skin Sensitisation, Buehler test).

Justification for type of information:

There is no study available elucidating the skin sensitisation potential of butyl ethyl ether (target substance). Therefore, a skin sensitisation study conducted with n-butyl ether was used in a read-across approach.
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because:
- structural similarity of the target and the source substances (the presence or absence of additional functional groups or substituents that could influence the behaviour of a chemical),
- similarity in physico-chemical profile of the source and target substances (MW, water solubility, partitioning behaviour (log Kow value))

Data source

Reference

Reference Type:

publication

Title:

Concentration-Dependent Elicitation of Dermal Sensitization in Guinea Pigs Treated with 2,4-Toluene Diisocyanate

Author:

Koschier F.J. et al.

Year:

1983

Bibliographic source:

TOXICOLOGY AND APPLIED PHARMACOLOGY 67, 401-407

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

Lower number of animals tested. Deviation in the days/duration.

GLP compliance:

not specified

Type of study:

Buehler test

Justification for non-LLNA method:

The Buehler test is an accepted method for hazard identification of skin sensitising substances as recommended in "ECHA guidance R.7a: Endpoint specific guidance".

Test material

Test material information

Constituent 1

Reference substance name:

Dibutyl ether

EC Number:

205-575-3

EC Name:

Dibutyl ether

Cas Number:

142-96-1

Molecular formula:

C8H18O

Specific details on test material used for the study:

not reported

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

not specified

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Young adult guinea pigs were received from either Hilltop Lab Animals, Inc. (Scottdale, Pa.) or Camm Breeding Laboratories, Inc. (Wayne. N.J.)
- Females (if applicable) nulliparous and non-pregnant: not specified
- Microbiological status of animals, when known: unknown
- Age at study initiation: Young adults
- Weight at study initiation: not specified
- Housing: individually in stainless-steel cages with wire-mesh bottoms
- Diet: Guinea Pig Chow 5026 (Ralston Purina Co.), ad libitum
- Water: ad libitum
- Acclimation period: not specified
- Indication of any skin lesions: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 40-60
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12
- IN-LIFE DATES: From: To: not specified

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, open

Vehicle:

other: n-butyl ether

Concentration / amount:

100 % n-butyl ether

Day(s)/duration:

24 hr

Challenge

Challenge 1

No.:

#1

Route:

epicutaneous, open

Vehicle:

other: n-butyl ether

Concentration / amount:

100% n-butyl ether

Day(s)/duration:

5 days

Challenge 2

No.:

#2

Route:

epicutaneous, open

Vehicle:

other: n-butyl ether

Concentration / amount:

100% n-butyl ether

Day(s)/duration:

14 days

No. of animals per dose:

5

Details on study design:

Please note, that due to the use of this publication for this study entry, only the results for n-butyl ether are relevant in the following.
n-butyl ether was used as vehicle. To exclude any reactions induced by n-butyl ether, a vehicle control was included in the test design (0.0 % test substance). This is documented in the results of the skin sensitizing test, where the application of n-butyl ether did not produce any significant reactions (refer to table 3 in section "Any other information on resulkts icl. tables") .

Details on study design:
The present study explored the quantitative dermal exposure requirements for dermal sensitization in the guinea pig in relation to the concentration required for dermal response at challenge. For induction, 2,4-TDI (DuPont, Wilmington, Del.; 97.5% minimum of 2,4-isomer and 2.5% maximum for 2,6-isomer) was dissolved in n-butyl ether to achieve concentrations of 4 to 40%. The animals in each induction group received a total application of 50.0 µL of solution with each animal receiving two 25-µL amounts on separate sites. Five days later, each guinea pig received six challenge applications of TDI in 25-µL aliquots. The challenge applications were on virgin sites and consisted of one n-butyl ether application and five TDI concentrations. Dermal irritation scores (modeled after Draize, 1965) for induction and challenge concentrations were determined on all animals (see Table 1 in section “Any other information on results incl. tables” below). The dermal responses elicited by the challenge application were most differentiable at the 24-hr reading (see Table 2 in section “Any other information on results incl. tables” below).
For the induced animals, Draize scores of 2.0 or higher at challenge were chosen as indicative of sensitization since very slight erythema was caused by the solvent. In some cases, a rechallenge was performed on animals 9 days after the first challenge. The procedures for the rechallenge were the same as those for the challenge.

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100 %

No. with + reactions:

4

Total no. in group:

5

Clinical observations:

Erythema

Results 2

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

Edema

Results 3

Group:

negative control

Remarks on result:

not measured/tested

Results 4

Group:

positive control

Remarks on result:

not measured/tested

Any other information on results incl. tables

A) Results of pilot test for determination of irritant concentration:

Please note, that due to the use of this publication for this endpoint record, the focus is only on the results of n-butyl ether (0.0% 2,4 -toluene diisocyanate).

Table 1: Primary skin irritation of 2,4 -toluene diisocyanate in n-butyl ether applied to naive animals^a

	Mean Draize irritation scores^bat
Application concentration (%)	24 hr	48 hr
0.00	1.0	0.0
0.025	1.0	0.8
0.050	0.6	0.0
0.10	1.0	1.0
0.20	1.0	1.0
0.40	1.0	0.8

^a Five guinea pigs each recieved the five application concentrations.

^b Maximum score in this system is 8; no individual scores were greater than1.0.

The criteria for the dermal scoring system were as follows:

Erythema formation	Value
No erythema	0
Very slight erythema (barely perceptible)	1
Slight erythema (but well defined)	2
Moderate erythema (but not severe)	3
Severe erythema (beet redness)	4
Total possible score	4

 

Edema formation	Value
No edema	0
Very slight edema (barely perceptible)	1
Slight edema (but well defined)	2
Moderate edema (but not severe)	3
Severe edema (beet redness)	4
Total possible score	4

Table 2: Primary skin irritation for the induction doses of 2,4 -toluene diisocyanate in n-butyl ether applied to naive animals^a

	Mean Draize irritation scores^bat
Application concentration (%)	24 hr	48 hr
0.0	1.0	0.2
8.0	1.4	1.6
20.0	2.0	2.0
40.0	2.0	2.0

^a Five guinea pigs recieved either a 0.0, 8.0, 20.0 or 40.0% TDI concentrations.

^b Maximum score in this system is 8.

B) Results of sensitisation tests:

Table 3: Dermal sensitization of animals induced with TDI^a

Induction application concentration (%)	Challenge concentration(%)
	0.00	0.025	0.050	0.10	0.20	0.40
	Mean scores 24 hr after Day 5 challenge^b
8.0	0.0	2.4	2.0	2.8	2.8	3.4
20.0	0.0	2.0	1.6	2.8	3.2	3.4
40.0	0.0	2.4	2.0	3.4	4.0	4.2
	Mean scores 24 hr after Day 14 challenge^b
0.0	0.0	0.5	0.9	0.6	0.0	0.4
8.0	0.0	1.6	1.8	2.4	3.6	3.2
20.0	0.0	1.6	2.0	2.8	4.6	4.2
40.0	0.0	2.0	2.2	2.6	4.2	4.0

^a The five guinea pigs which recieved induction application of either 0.0, 8.0, 20.0 or 40.0% TDI were challenged with 25µL of TDI.

^b Maximum score in this system is 8.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results reported in the present study n-butyl ether is not considered to be a skin sensitizer.

Executive summary:

The present study explored the quantitative dermal exposure requirements for dermal sensitization in the guinea pig in relation to the concentration required for dermal response at challenge.

In this dermal sensitisation study (equivalent to OECD 406) guinea-pigs of the Hartley strain were tested. Test animals were challenged 5 days after induction. n-Butyl ether was used as vehicle. To exclude any reactions induced by n-butyl ether, a vehicle control was included in the test design (0.0 % test substance). At the 24-h reading no dermal reactions were seen in the vehicle application. Based on the results, n-butyl ether is not a dermal sensitiser.