Glutaral

Respiratory sensitisation

Administrative data

Endpoint:

respiratory sensitisation: in vivo

Remarks:

IgE Test

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Four mice were tested with each of the dose levels (0, 5, 10, 25, 50%) to determine proliferative activity in a Local Lymph Node assay.

GLP compliance:

no

Type of study:

mouse local lymph node assay (LLNA)

Specific details on test material used for the study:

50% glutaraldehyde in water

Species:

mouse

Strain:

Balb/c

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Olac Ltd., Oxfordshire
- Sex: Females
- Age at study initiation: 6-8 weeks old
- Weight at study initiation: not reported
- Housing: each dose group (4) housed together
- Diet (e.g. ad libitum): not reported
- Water (e.g. ad libitum): not reported
- Indication of any skin lesions: no

ENVIRONMENTAL CONDITIONS
None reported

Vehicle:

other: acetone

Concentration:

0, 5, 10, 25, and 50% w/v in acetone

No. of animals per dose:

4

Details on study design:

Control animals: Yes, vehicle controls (acetone)

Animals were dosed on the dorsum of both ears daily for three consecutive days. On the 6th day, mice were injected intravenously with 3H-methyl thymidine. Five hours later, mice were sacrificed. No challenge, scoring schedule or removal of the test substance.

Parameter:

SI

Value:

15.5

Test group / Remarks:

5%

Parameter:

SI

Value:

23.4

Test group / Remarks:

10%

Parameter:

SI

Value:

38.7

Test group / Remarks:

25%

Parameter:

SI

Value:

34.9

Test group / Remarks:

50%

Cellular proliferation data / Observations:

Each of the test concentrations produced substantial levels of lymph node cell proliferative activity. Increasing concentrations of the test material elicited stimulation indices of 15.5, 23.4, 38.7, and 34.9 respectively. The data confirms that the test material produces skin sensitization potential. An EC3 was not calculated.

Table 2

Activity of 50% Glutaraldehyde in the Local Lymph Node Assay

Concentration	Dpm/node x 10e-2	Stimulation Index
0	2.36	-
5	36.70	15.5
10	55.35	23.4
25	91.45	38.7
50	82.57	34.9

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

Test material possesses skin and respiratory tract sensitization potential.

Executive summary:

Four mice, were tested with each of the dose levels (0, 5, 10, 25, 50%), each group was housed together. Animals were dosed on the dorsum of both ears daily for three consecutive days. On the 6th day, mice were injected with 3H-methyl thymidine in phosphate buffered saline. Five hours later, mice were sacrificed and the draining auricular lymph nodes were removed and pooled for the experimental group. A single cell suspension of lymph node cells was prepared by mechanical disaggregation through a stainless steel gauze. Pooled LNC were washed, and resuspended 12 hours later in TCA prior to transfer into scintillation fluid. Incorporation of 3H-TdR was measured by beta-scintillation counting and expressed as mean disintegrations per minute per node for each test group. The activity of each test group was divided by the activity of the vehicle control group to give a test/control ratio for each concentration tested.

 

Each of the test concentrations produced substantial levels of lymph node cell proliferative activity. Increasing concentrations of the test material elicited stimulation indices of 15.5, 23.4, 38.7, and 34.9 respectively. The data confirms that the test material produces skin sensitization potential. An EC3 was not calculated.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Groups of 6 mice were shaved on flanks and dosed dermally with 50 µL of test material. Seven days later, the animals were dosed again with the same test material at half the first concentration applied to the dorsum of both ears. Fourteen days later, mice were sacrificed, and the concentration of serum IgE was measured.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glutaral

EC Number:

203-856-5

EC Name:

Glutaral

Cas Number:

111-30-8

Molecular formula:

C5H8O2

IUPAC Name:

glutaraldehyde

Test material form:

liquid

Specific details on test material used for the study:

50% glutaraldehyde in water

Test animals

Species:

mouse

Strain:

Balb/c

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Olac Ltd., Oxfordshire
- Sex: Females
- Age at study initiation: 6-8 weeks old
- Weight at study initiation:not reported
- Housing: each dose group (4) housed together
- Diet (e.g. ad libitum): not reported
- Water (e.g. ad libitum): not reported
- Indication of any skin lesions: no

ENVIRONMENTAL CONDITIONS
None reported

Test system

Route of induction exposure:

dermal

Route of challenge exposure:

other: dorsum of both ears

Vehicle:

other: acetone

Concentration:

0, 2.5, 5 and 12.5 % w/v in acetone

No. of animals per dose:

6

Details on study design:

TREATMENT PREPARATION AND ADMINISTRATION: Groups of mice (6) were shaved on flanks and dosed dermally with 50 µL of test material. Seven days later, the animals were dosed again with the same test material at half the first concentration applied to the dorsum of both ears. Fourteen days later, mice were sacrificed.

Concentrations used for Induction: 50 μl of 0, 5, 10 and 25% w/v in acetone

Concentrations used for Challenge: 25 uL of 0, 2.5, 5, 12.5% w/v in acetone.

There was no re-challenge, scoring schedule or removal of the test substance.

Challenge controls:

vehicle controls (acetone), positive control (trimellitic anhydride, TMA), and negative chemical allergen control (2,4-dinitrochlorobenzene, DNCB)

Positive control substance(s):

trimellitic anhydride (TMA)

Negative control substance(s):

2,4-dinitrochlorobenzene (DNCB)

Results and discussion

Results:

Exposure of mice to glutaraldehyde resulted in a dose-dependent increase in serum IgE relative to the control, elicitating mean values of 1.280 +/- 0.193 ug/m. A substantial increase in serum IgE levels relative to the historical control is considered indicative of the potential to cause sensitization of the respiratory tract. The data leads to the conclusion that glutaraldehyde exhibits some capacity for sensitization of the respiratory tract.

Any other information on results incl. tables

Table 3

Activity of 50% Glutaraldehyde in the Mouse IgE Test

Chemical	Serum IgE Concentration mean ± SE μg/ml
AOO	0.262 ± 0.022
DNCB (1% w/v)	0.212 ± 0.042
TMA (25% w/v)	1.991 ± 0.160
Acetone	0.304 ± 0.024
Glutaraldehyde (5% w/v)	0.516 ± 0.038
Glutaraldehyde (10% w/v)	0.640 ± 0.195
Glutaraldehyde (25% w/v)	1.280 ± 0.193
Untreated Mice	Range = 0.115-0.595

AOO- 4:1 acetone: olive oil

DNCB- 2,4 -dinitrochlorobenzene

TMA- trimellitic anhydride

Applicant's summary and conclusion

Interpretation of results:

other: test material exhibits capacity for sensitization of the respiratory tract.

Conclusions:

Glutaraldehyde is considered to be a respiratory sensitizer under conditions of the test.

Executive summary:

Groups of mice (6) were shaved on flanks, and dosed dermally with 50 µL of test material. Seven days later, the animals were dosed again with the same test material at half the first concentration applied to the dorsum of both ears. Fourteen days later, mice were sacrificed, and blood was collected and serum prepared. The concentration of serum IgE (measured using a sandwich ELISA) was compared to the responses of the positive control (trimellitic anhydride) and negative control (DNCB). Results were expressed as serum IgE concentration (µg/mL).

 

Exposure of mice to the test material resulted in a dose-dependent increase in serum IgE relative to the control, elicitating mean values of 1.280 ± 0.193 µg/mL. A substantial increase in serum IgE levels relative to the historical control is considered indicative of the potential to cause sensitization of the respiratory tract. The data leads to the conclusion that glutaraldehyde exhibits some capacity for sensitization of the respiratory tract.