3-methoxy-3-methylbutan-1-ol

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1976

Materials and methods

Test guideline

Qualifier:

equivalent or similar to

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

yes

Remarks:

Minimal reporting of test animals and husbandry, of test substance informations, of inhalation chamber, of exposure data and test conditions. It has not been tested on both sexes, just on male.

Principles of method if other than guideline:

test animals only male, no female /
by using a whole-body mode of exposure no deteails of animals’ breathing zone in an inhalation chamber /
minimal reporting of inhalation chamber - volume" of the test animals should not exceed 5% of the chamber volume /
for 6 hours per day on a 5 day per week basis for a period of 4 weeks / no details of housing conditions and feed of the test animals during the exposure time // no data about measured actual chamber concentration during exposure time /minimal reporting of exposure data - no data about nominal and actual concentrations from the test concentrations in the inhalation chamber
minimal reporting of test conditons
Test animals and husbandry

GLP compliance:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Name of test material (as cited in study report): MMB
- Molecular formula (if other than submission substance):
- Molecular weight (if other than submission substance):
- Smiles notation (if other than submission substance):
- InChl (if other than submission substance):
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type:
- Physical state: colorless and transparent liquid
- Analytical purity:
- Impurities (identity and concentrations):
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date:
- Lot/batch No.:
- Expiration date of the lot/batch:
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions:
- Storage condition of test material:
- Other:

Test animals

Species:

rat

Strain:

other: JCL-SD

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Age at study initiation: 6 weeks
- Diet (e.g. ad libitum): Pellet chow CE-2 (CLEA Japan, Inc.) ad libitum
- Water (e.g. ad libitum): municipal tap water ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 0.5°C
- Humidity (%): 60 ± 5%

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

not specified

Details on inhalation exposure:

a total of 20 doses within 4 successive weeks.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

none given

Duration of treatment / exposure:

4 weeks

Frequency of treatment:

4 hours/day, five times/week

Doses / concentrations

Remarks:

Doses / Concentrations:
100, 300, 500 ppm
Basis:
nominal conc.

No. of animals per sex per dose:

10 (male)

Control animals:

yes

Details on study design:

Post-exposure period: None

Positive control:

none

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS and DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Observation including behavior and general condition was performed on all the
animals daily

BODY WEIGHT: Yes
- Time schedule for examinations: After the experiment initiation, body weight of all animals was determined before inhalation exposure at the rate of three times a week in the first two weeks (every other day), afterwards, twice a week (Tuesday and Friday). Moreover, weight gain index was calculated (the weight at the time of the experiment initiation is based to be 100).

WATER CONSUMPTION and FOOD CONSUMPTION:
- The total weight of each feeder and each water-supply bottle were measured every other day and the difference between last measurement value and latest measurement value was regarded as the daily food or water consumption.

OPHTHALMOSCOPIC EXAMINATION:No data

HAEMATOLOGY and CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: after completion of inhalation exposure experiments (for 20 times)
- Anaesthetic used for blood collection: Yes (pentobarbital sodium)
- Animals fasted: No data
- How many animals: all test animals and control animals
- Parameters checked in table [No. 1 - 4] were examined.

URINALYSIS: Yes
- The urine was collected at necropsy and the parameters listed below were examined using Multistix (Ames corporation).
Protein, Glucose, pH, Ketone, Bilirubin, Urobilinogen.

NECROPSY: Yes
- Macroscopical change was examined for thoracic cavity, organs in abdominal cavity at necropsy. Then, each organ was removed and the weight of the organs was measured. The ratio to the body weight (relative weight) was calculated using numerical
formula below.
Relative weight = organ weight / body weight x 100 (%)

NEUROBEHAVIOURAL EXAMINATION: No data

HISTOPATHOLOGICAL EXAMINATION:
- The following organs were collected from the animals immediately after the completion of necropsy, fixed in a neutral phosphate-buffered formalin solution and dehydrated to prepare 4 µm paraffin sections, and a microscopic examination was performed by hematoxylin eosin (HE) stain:
Liver, Kidney, Adrenal gland, Spleen, Heart, Lung, Brain and spinal cord, Testis

Sacrifice and pathology:

HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Description (incidence and severity):

No statistically significant changes

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

No statistically significant changes

Water consumption and compound intake (if drinking water study):

no effects observed

Description (incidence and severity):

No statistically significant changes

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

An increase of GOT in 100 and 500 ppm.

Urinalysis findings:

no effects observed

Description (incidence and severity):

No statistically significant change

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Increases of absolute and relative weights of kidney in all treated groups

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

No effect related to the test material

Details on results:

CLINICAL SIGNS AND MORTALITY
There were no atypical signs noted throughout the study in any animals.

BODY WEIGHT AND WEIGHT GAIN
All animals gained weight normally and neither delay of weight gain nor weight loss were noted during the study period. No significant difference from the control group was noted in any of the experimental group.

WATER CONSUMPTION and FOOD CONSUMPTION
In both food consumption and water consumption, no significant difference from the control group was noted in any of the experimental group.

HAEMATOLOGY and CLINICAL CHEMISTRY
The GOT activity in 500 ppm and 100 ppm exposure groups were significantly higher than that of control group (500 ppm exposure group was significantly different at p<0.05 (significance at 95% or above), 100 ppm exposure group was significantly different at p<0.01). In 500 ppm exposure group, one animal showed the remarkable high value of the GOT and GPT activity and one animal showed the remarkable high value of the GOT activity only. In other parameter, no significant difference from the control group was noted in any of the experimental group.

URINALYSIS
In all experimental parameter, no significant difference from the control group was noted in any of the experimental group.

ORGAN WEIGHTS
Although significantly higher values of absolute and relative kidney weights were observed in all experimental groups compared with control groups, there was no significant difference among three experimental groups. In other organs, no significant difference from the control group was noted in any of the experimental group.

NECROPSY
In many animals of all groups including control, slight congestion was observed in lung. (Often observed generally. Not the effect of MMB.) However no macroscopical abnormalities were noted in any other organs.

HISTOPATHOLOGY
Liver
Minute focal hepatic necrosis with slight cellular infiltration and/or debris of cell nucleus was noted in 1 animal of 500 ppm and 300 ppm exposure group, respectively, and in 2 animals of 100 ppm exposure group. It was seen in 1-2 places under the membrane and there was no MMB dose relationships in incidence of this finding. Nodule of round cell in sinusoid or Grisson's Capsule was noted in 6 animals of 500 ppm exposure group, in 7 animals of 300 ppm group, 9 animals of 100 ppm group and 9 animals of control group. This finding was considered to be the extramedullary hematopoiesis, therefore it is considered not to be pathological findings.

Kidney
The minute fibrosis of the cortex (just under the membrane) was noted in 2 animals in both of 500 ppm and 300 ppm exposure group, respectively, in 3 animals of 100 ppm exposure group and in 1 animal of the control group. In these areas, slight local fibrosis was noted and dilatation like cysts was also seen in renal tubule included in these area. The focal lymphocyte infiltration in stroma of the renal cortex (slight) was noted in 1 animal in both of 500 ppm and 300 ppm exposure group, respectively. On the other hands, slight lymphocyte infiltration was noted from mucous membrane of renal pelvis to medulla in 1 animal of the control group. However, glomerulus and uriniferous tubule showed no toxicologically relevant change.

Spleen
In many animals of all groups, congestion was noted. With the exception of congestion, no remarkable changes were noted.

Lung
In both of 500 ppm exposure group and control group, a few small hemorrhagic spots in lung parenchyma were noted in 1 animal, respectively.

Others
No remarkable abnormal findings were noted in testes, heart, adrenal gland, brain and spinal cord.

Effect levels

1

Dose descriptor:

LOAEC

Effect level:

100 ppm

Sex:

male

2

Dose descriptor:

LOAEC

Effect level:

530 mg/m³ air (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: based on 5.3 g/l vapour weight calculated from above

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 1: Hematological examination/Biochemical examination [500 ppm]

Number	red blood cell	ehite blood cell	packed cell volume	hemoglobin	serum total protein	GOT	GPT	ALP	BUN
	10^4/ mm^3	/mm^3	%	g/dl	g/dl	Karmen	Karmen	King-armstrong	mg/dl
1	626	7550	42.0	13.1	6.0	-	-	-	-
2	608	5500	41.5	13.1	5.6	-	-	-	-
3	591	5750	42.0	13.9	5.4	72.0	27.0	35.1	19.5
4	706	5150	42.5	13.4	5.5	61.0	23.0	31.7	19.5
5	647	7450	40.5	13.1	5.4	62.0	22.0	42.0	18.7
6	543	6900	41.0	12.9	5.3	107.0	37.0	24.8	27.0
7	569	10200	40.0	12.6	5.1	80.5	40.0	32.8	25.9
8	583	7100	40.0	12.9	5.4	121.0	88.5	40.7	22.7
9	623	10200	40.0	13.1	5.4	65.0	27.5	37.8	24.1
10	577	5750	39.0	12.8	5.0	86.0	44.0	35.0	18.7
Mean	607	7155	40.9	13.1	5.4	81.8	38.6	35.0	22.0
S.D.	44	1719	1.1	0.3	0.3	20.6	20.3	5.1	3.2

Table 2: Hematological examination/Biochemical examination [300 ppm]

Number	red blood cell	ehite blood cell	packed cell volume	hemoglobin	serum total protein	GOT	GPT	ALP	BUN
	10^4/ mm^3	/mm^3	%	g/dl	g/dl	Karmen	Karmen	King-armstrong	mg/dl
11	645	6000	41.0	13.2	6.0	59.0	20.0	35.3	16.9
12	654	7400	44.0	14.0	6.4	86.0	29.0	41.8	19.5
13	698	7250	43.0	13.7	5.9	59.5	22.0	43.6	17.0
14	546	4900	43.5	12.9	5.0	70.0	20.0	31.7	18.7
15	581	5450	40.5	12.9	5.4	62.0	18.0	42.0	21.4
16	618	7750	40.5	13.1	5.4	75.0	31.0	21.9	22.5
17	596	7450	40.0	13.3	5.4	-	-	-	-
18	614	9250	42.5	13.3	5.4	81.5	37.0	33.0	16.5
19	584	7050	38.5	12.6	5.0	66.0	30.5	36.3	20.8
20	611	8750	39.5	13.1	5.0	63.0	26.0	32.8	18.7
Mean	615	7125	41.3	13.2	5.5	69.1	25.9	35.4	19.1
S.D.	41	1295	1.7	0.4	0.5	9.2	6.0	6.3	2.0

Table 3: Hematological examination/Biochemical examination [100 ppm]

Number	red blood cell	ehite blood cell	packed cell volume	hemoglobin	serum total protein	GOT	GPT	ALP	BUN
	10^4/ mm^3	/mm^3	%	g/dl	g/dl	Karmen	Karmen	King-armstrong	mg/dl
21	738	6900	42.5	13.8	6.0	68.0	20.0	41.8	22.0
22	601	8700	40.5	13.2	6.0	86.0	30.0	42.7	18.2
23	623	8100	43.5	14.4	6.0	90.0	24.0	35.6	16.9
24	632	7600	41.0	14.1	5.4	67.5	20.0	31.7	14.4
25	689	6700	42.5	14.0	5.4	82.5	32.0	32.6	18.7
26	591	8250	40.5	12.6	5.0	72.5	36.5	38.8	19.0
27	599	7200	38.0	12.5	5.4	66.0	34.0	36.5	20.7
28	551	7950	41.0	13.1	5.3	82.5	37.5	38.4	20.1
29	592	6100	40.0	13.2	5.5	74.0	33.0	38.5	21.5
30	642	8500	40.5	13.5	5.0	59.5	30.5	32.4	14.4
Mean	626	7600	41.0	13.4	5.5	74.9	29.8	36.9	18.6
S.D.	51	808	1.5	0.6	0.4	9.4	6.0	3.7	2.6

Table 4: Hematological examination/Biochemical examination [control group]

Number	red blood cell	ehite blood cell	packed cell volume	hemoglobin	serum total protein	GOT	GPT	ALP	BUN
	10^4/ mm^3	/mm^3	%	g/dl	g/dl	Karmen	Karmen	King-armstrong	mg/dl
31	692	5550	40.5	13.7	5.8	53.0	25.0	23.0	16.9
32	617	10850	41.5	13.5	5.7	72.0	27.0	37.5	21.9
33	582	9600	43.0	14.2	6.3	57.5	18.0	38.5	18.5
34	614	6150	41.0	13.7	5.3	59.0	21.5	36.0	18.1
35	726	7450	44.0	14.4	6.0	65.0	24.5	31.5	20.0
36	630	7650	39.5	12.8	5.4	64.5	28.0	35.8	21.2
37	662	9250	40.0	13.1	5.9	69.5	35.5	36.6	15.5
38	608	6500	40.0	13.2	5.2	69.0	27.0	25.7	18.5
39	598	8650	40.5	13.1	5.1	60.0	23.0	35.6	28.9
40	686	6000	39.5	13.4	5.4	57.0	23.5	30.2	14.1
Mean	642	7765	41.0	13.5	5.6	62.7	25.3	33.0	19.8
S.D.	45	1680	1.4	0.5	0.4	6.0	4.4	5.0	3.7

Table 5: Absolute organ weight/Relative organ weight [500ppm]

Number	Liver		Kidney		Spleen		Brain		Testis		Lung		Adrenal gland		Heart
	g	%	g	%	g	%	g	%	g	%	g	%	g	%	g	%
1	14.978	4.243	2.819	0.799	0.948	0.269	1.906	0.540	3.148	0.892	1.596	0.452	0.049	0.014	1.145	0.324
2	13.323	4.298	2.647	0.854	0.831	0.268	1.828	0.590	3.019	0.974	1.360	0.439	0.051	0.016	0.977	0.315
3	13.635	4.342	2.535	0.807	0.726	0.231	1.891	0.602	3.184	1.014	1.369	0.436	0.052	0.017	1.089	0.347
4	15.046	4.559	2.673	0.810	1.016	0.308	1.863	0.565	3.182	0.964	1.489	0.451	0.056	0.017	1.248	0.378
5	15.010	4.276	2.757	0.785	0.755	0.215	1.897	0.540	2.932	0.835	1.622	0.462	0.050	0.014	1.167	0.332
6	16.275	4.690	2.502	0.721	0.970	0.280	1.833	0.528	2.927	0.844	1.550	0.447	0.051	0.015	1.062	0.306
7	15.366	4.428	2.820	0.813	0.902	0.260	1.852	0.534	3.221	0.928	1.578	0.455	0.062	0.018	0.991	0.286
8	16.919	4.674	2.779	0.768	1.154	0.319	1.881	0.520	3.156	0.872	1.706	0.471	0.060	0.017	0.982	0.271
9	15.783	4.409	2.732	0.763	0.846	0.236	1.861	0.520	3.001	0.838	1.515	0.423	0.051	0.014	1.127	0.315
10	14.917	4.400	2.874	0.848	0.978	0.288	1.907	0.563	3.226	0.952	1.635	0.482	0.056	0.017	1.044	0.308
Arithmetic Mean	15.125	4.432	2.714	0.797	0.913	0.267	1.872	0.550	3.100	0.911	1.542	0.542	0.054	0.016	1.083	0.318
S.D	1.029	0.151	0.117	0.038	0.122	0.032	0.027	0.027	0.111	0.061	0.106	0.016	0.004	0.001	0.85	0.029

g: absolute organ weight

%: relative weight

Table 6: Absolute organ weight/Relative organ weight [300ppm]

Number	Liver		Kidney		Spleen		Brain		Testis		Lung		Adrenal gland		Heart
	g	%	g	%	g	%	g	%	g	%	g	%	g	%	g	%
11	16.442	4.480	2.719	0.741	0.817	0.226	1.919	0.523	3.095	0.843	1.565	0.426	0.064	0.017	1.072	0.292
12	13.745	4.140	2.498	0.752	0.794	0.239	1.885	0.568	2.918	0.879	1.565	0.471	0.054	0.016	0.989	0.298
13	13.042	4.127	2.244	0.710	0.719	0.228	1.999	0.633	3.165	1.002	1.461	0.462	0.041	0.013	0.974	0.308
14	15.517	4.346	2.739	0.767	1.037	0.290	1.917	0.537	3.059	0.857	1.396	0.391	0.058	0.016	0.997	0.279
15	14.746	4.262	2.868	0.829	0.792	0.229	1.891	0.547	2.978	0.861	1.407	0.407	0.040	0.012	1.051	0.304
16	15.906	4.637	2.884	0.841	0.813	0.237	1.907	0.556	3.230	0.942	1.443	0.421	0.048	0.014	1.022	0.298
17	15.012	4.377	2.975	0.867	0.952	0.278	1.915	0.558	3.450	1.006	1.610	0.469	0.054	0.016	1.073	0.313
18	15.648	4.408	3.105	0.875	0.789	0.222	1.994	0.562	3.192	0.899	1.498	0.422	0.055	0.015	1.145	0.323
19	15.640	4.258	2.775	0.760	0.916	0.251	1.875	0.514	2.976	0.815	1.621	0.444	0.050	0.014	1.075	0.295
20	17.861	4.651	2.696	0.702	1.123	0.292	1.892	0.493	3.378	0.880	1.713	0.446	0.055	0.014	1.129	0.294
Arithmetic Mean	15.346	4.369	2.750	0.784	0.875	0.249	1.919	0.549	3.144	0.898	1.528	0.436	0.052	0.015	1.053	0.300
S.D	1.278	0.173	0.231	0.060	0.122	0.026	0.041	0.036	0.166	0.062	0.098	0.026	0.007	0.001	0.055	0.012

g: absolute organ weight

%: relative weight

Table 7: Absolute organ weight/Relative organ weight [100ppm]

Number	Liver		Kidney		Spleen		Brain		Testis		Lung		Adrenal gland		Heart
	g	%	g	%	g	%	g	%	g	%	g	%	g	%	g	%*
21	15.747	4.845	2.528	0.778	0.984	0.303	1.897	0.584	2.819	0.867	1.513	0.466	0.044	0.014	0.997	0.3
22	15.326	4.774	2.717	0.846	0.898	0.280	1.890	0.589	2.798	0.872	1.319	0.411	0.043	0.013	0.990	0.3
23	16.049	4.585	2.751	0.786	0.901	0.257	1.972	0.563	2.857	0.816	1.469	0.420	0.052	0.015	1.148	0.3
24	14.356	4.044	2.491	0.702	0.904	0.255	1.763	0.479	2.729	0.769	1.446	0.407	0.061	0.017	1.046	0.2
25	15.000	4.323	2.531	0.729	0.933	0.269	1.869	0.539	3.490	1.006	1.321	0.381	0.060	0.017	1.053	0.3
26	14.867	4.334	2.679	0.781	0.929	0.271	1.860	0.542	3.218	0.938	1.418	0.413	0.051	0.015	1.128	0.3
27	15.757	4.414	2.631	0.737	0.768	0.215	1.920	0.538	3.042	0.852	1.549	0.434	0.050	0.014	1.044	0.2
28	14.777	4.234	2.395	0.686	0.663	0.190	1.859	0.533	2.997	0.859	1.411	0.404	0.052	0.015	1.006	0.2
29	16.977	4.651	2.525	0.692	0.788	0.216	1.929	0.528	3.429	0.939	1.595	0.437	0.063	0.017	1.025	0.2
30	13.903	3.972	2.876	0.822	0.921	0.263	1.988	0.568	2.476	0.707	1.578	0.451	0.064	0.018	1.146	0.3
Arithmetic Mean	15.276	4.418	2.612	0.756	0.869	0.252	1.895	0.546	2.986	0.863	1.462	0.422	0.054	0.016	1.058	0.3
S.D	0.846	0.279	0.137	0.052	0.093	0.033	0.061	0.030	0.302	0.082	0.093	0.024	0.007	0.002	0.058	0.01

g: absolute organ weight

%: relative weight

*In the copy of the original study, the last two digits behind the comma could not be identified.
Cause there are no abnormality findings in the study on the heart, this data gap is negligible and therefore does not lead to a deterioration of the results of this study

Table 8: Absolute organ weight/Relative organ weight [control group]

Number	Liver		Kidney		Spleen		Brain		Testis		Lung		Adrenal gland		Heart
	g	%	g	%	g	%	g	%	g	%	g	%	g	%	g	%
31	15.710	4.540	2.412	0.697	0.722	0.209	1.945	0.562	3.194	0.923	1.501	0.434	0.049	0.014	1.043	0.301
32	16.429	4.861	2.327	0.688	1.102	0.328	1.795	0.531	1.075	0.318	1.656	0.490	0.049	0.014	1.027	0.304
33	16.141	4.521	2.386	0.668	1.049	0.294	1.840	0.515	3.151	0.883	1.534	0.430	0.063	0.018	1.014	0.284
34	12.400	3.792	2.092	0.640	0.714	0.218	1.773	0.542	2.127	0.650	1.411	0.431	0.050	0.015	0.798	0.299
35	15.653	4.397	2.343	0.658	0.889	0.250	1.835	0.515	3.209	0.901	1.479	0.415	0.053	0.015	1.121	0.315
36	14.892	4.231	2.470	0.702	0.815	0.232	2.005	0.570	3.029	0.861	1.574	0.447	0.057	0.016	1.049	0.298
37	15.694	4.014	2.762	0.706	0.921	0.236	1.852	0.474	2.662	0.681	1.630	0.417	0.049	0.013	1.061	0.271
38	12.952	3.669	2.391	0.677	0.800	0.227	1.986	0.563	3.227	0.914	1.479	0.419	0.047	0.013	1.200	0.340
39	14.818	4.071	2.747	0.755	0.900	0.247	1.922	0.528	3.244	0.891	1.633	0.449	0.046	0.013	1.139	0.313
40	14.639	4.000	2.449	0.669	1.013	0.277	1.877	0.513	3.329	0.910	1.544	0.422	0.053	0.014	1.068	0.292
Arithmetic Mean	14.933	4.210	2.438	0.686	0.893	0.252	1.883	0.531	2.825	0.793	1.544	0.435	0.052	0.015	1.052	0.302
S.D	1.259	0.351	0.187	0.030	0.126	0.035	0.075	0.028	0.678	0.184	0.075	0.021	0.005	0.002	0.101	0.018

g: absolute organ weight

%: relative weight

Applicant's summary and conclusion

Conclusions:

The male rats were exposed to 500, 300 and 100 ppm 3-methyl-3-methoxybutanol by inhalation for 4 hours a day, 5 days a week (total 20 times of inhalation. Although no severe effect in the animals was noted, the serum transaminase (GOT) activity and absolute and relative kidney weights of the experimental groups were significantly higher than those of control group. As the results, it was considered that liver and kidney were slightly affected by MMB.

Executive summary:

Inhalation exposure to MMB at the concentrations of 500, 300 and 100 ppm for 4 hours a day, 5 days a week (total 20 times of inhalation) produced following findings in male rats.

1) GOT activity in 500 ppm and 100 ppm exposure groups was significantly higher than that of control group.

2) The Absolute and relative kidney weights in all exposure groups were significantly higher than that of control group. However no abnormal findings were noted in liver histopathologically and except for GOT activity, liver function tests showed no abnormalities. Regarding kidney, there was no significant difference between each experimental group and control group in each functional examination and no toxicological relevant change was noted in histopathological examinations.

These results were summarized as follows.

It is considered that under this experiment condition, although MMB exposure slightly affected liver and kidney, MMB exposure caused no severe effect in organs. Therefore, it is necessary to pay attention enough if there is a possibility to inhale MMB for a long time. The chemical’s action to the living body may be different according to the animal species. It would be desirable to examine the influence of this material to the living body further in the greater detail by long term experiment.