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Carcinogenicity

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Description of key information

Long Evans hooded rats were exposed by inhalation to 9-27 ppm diethylhydroxylamine and the vapor of diethylamine hydrogen sulfite (Heicklen et al., 1981). In one of 3 test chambers each containing 45-49 rats, the rats were also exposed to 9 ppm of nitroethane. Very early 1 test animal developed a hemangioendothelioma, but no additional ones developed later. Examinations for animals exposed >1 year indicated no significant differences between the control and test groups, except for interstitial cell tumors of the testes which showed up in 4 of the 47 exposed males that were examined compared to 0 in the 25 control males. However, this incidence (8.5%) is too small to establish any definite conclusion.

Swiss strain mice were subjected to inhalation of 10.3 ppm diethylhydroxylamine, 10.1 ppm nitroethane, and vapors of diethylamine hydrogen sulfite for >2 year (Heicklen et al., 1982). Histopathological evaluation of all organs indicated only a few significant findings. The incidence of all tumors, as well as subcutaneous tumors (principally fibrosarcomas), increased in exposed males with marginal significance. The incidence of any tumors in exposed females decreased with marked statistical significance.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
carcinogenicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Technical and protocol deficiences in this study preclude the use of this data to unequivocally evaluate the carcinogenicity and chronic potential of DEHA
Reason / purpose:
reference to same study
Principles of method if other than guideline:
Rats were exposed by inhalation to diethylhydroxylamine and the vapor of diethylamine hydrogen sulfite. In one of three test chambers, the rats were also exposed to nitroethane. In the first12 months of the experiment two males and two females from both the control chamber and the chamber containing all three gases were sacrificed at 3-month intervals. After the first year only moribund animals were sacrificed except at the very end of the study when all remaining animals were sacrificed.
GLP compliance:
no
Species:
rat
Strain:
Long-Evans
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc.
- Age at study initiation: 6-8½ weeks old

ENVIRONMENTAL CONDITIONS
No data
Route of administration:
inhalation
Type of inhalation exposure (if applicable):
whole body
Vehicle:
air
Details on exposure:
Chamber exposure:
The exposure system consisted of two hexagonal exposure chambers, an air prefilter, a positive displacement rotary blower, and a pollutant injection apparatus. The chambers were fabricated of stainless steel. They each have a volume of ca. 1250 liters. Air is drawn from a temperature- and humidity-controlled room by the blower. The air enters through a Chemical-Biological-Radiological filter and passes through both chambers connected in parallel. Sufficient flow is maintained to effect ca. 13 air changes per hour. A slight negative pressure (ca. 0.25 in. H2O) is created to insure that any leakage will be inward.

Atmosphere generation:
Dry, prepurified air is bubbled through the liquids and saturated with these compounds. The liquids are maintained at 0°C to prevent aerosol formation. The flow through each saturator is controlled to obtain the proper chamber concentration as determined by flowmeter readings. The saturator outputs are mixed and injected into the bulk air flow at the top of the second chamber. The diethylamine hydrogen sulfite oil produced in the DEHA-SO2 reaction has very little vapor pressure (< 10-3 Torr). It was placed in second chamber in a ventilated container where it is permitted to evaporate freely.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Absolute measurements of DEHA and nitroethane concentrations were performed on air samples taken from the center of each test chamber through a Teflon tube. The sample was allowed to expand into an evacuated 12-liter bulb. Part of the bulb sample was introduced into a 40-m-long path IR cell mounted on a Beckman Model IR-10 for the DEHA analysis. The band associated with the C-H stretch and centered at 2995 cm-1 was used for the analysis.
ln the early stages of the study absolute analyses were performed at least once a day. Over a period of 2 weeks these readings varied by Iess than 5% from the values obtained from the flow-meter readings for DEHA and nitroethane. Therefore, after this initial period, absolute analyses were performed only twice a week, then reduced to once a week, and finally to once every few months, after it became clear that there was no difference from the flow-meter readings
Duration of treatment / exposure:
Life time, at least 24 months
Frequency of treatment:
- DEHA and Nitroethane: chamber 4: 12 hr a day, 6 days a week for 5 months then 7 hr a day, 5 days a week. Chamber 1 and 2: 7 hr a day, 5 days a week
- Diethylamine hydrogen sulfite: chamber 4: 24 hr a day, 7 days a week
Post exposure period:
None
Remarks:
Doses / Concentrations:
DEHA 16±3 ppm + diethylamine hydrogen sulfite < 1 ppm
Basis:
other: analytical conc., chamber 1
Remarks:
Doses / Concentrations:
DEHA 12-27 ppm + diethylamine hydrogen sulfite < 1
Basis:
other: analytical conc., chamber 2
Remarks:
Doses / Concentrations:
DEHA 9 ppm + Nitroethane 9±2 ppm + diethylamine hydrogen sulfite < 1 ppm
Basis:
other: analytical conc., chamber 4
No. of animals per sex per dose:
Exposed: 27-24 males and 18-24 females.
Control:25 males and 18 females
Control animals:
yes, sham-exposed
Details on study design:
Initially two groups of animals were exposed, a control group in chamber 3 and a test group in chamber 4. For the first year at 3-month intervals, two males and two females in each chamber were sacrificed. Hematology, blood chemistry, and gross and microscopic postmortem examinations were done on these animals.
At the 3-month exposure, one exposed male had a malignant skin tumor which was characterized as a hemangioendothelioma. Because of this finding so early in the study, it was decided to increase the number of exposed animals, and chambers 1 and 2 were brought into the study about 6 months after the initiation of exposure in chambers 3 and 4.
Since at about 12 months exposure, natural deaths were beginning to occur, no more healthy animals were sacrificed. Only chose animals which were moribund were killed except at the completion of the study, when all remaining animals were sacrificed.
Observations and examinations performed and frequency:
- Body weight: recorded after sacrifice and removal of blood
- Food consumption: no
- Water consumption: no
- Clinical signs: no
- Mortality:
- Macroscopic examination:
- Ophthalmoscopic examination: no
- Haematology: Red blood cell count, total and differential white blood cell counts, red blood cell indices, and morphology.
- Clinical chemistry: total protein. globulin, albumin, serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum calcium, serum phosphorus, blood urea nitrogen, creatinine and blood glucose. After the 6-month sacrifice. tests were also made for total bilirubin and cholesterol.
- Urinalysis: no
Sacrifice and pathology:
ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC):
Microscopic postmortem examination of tissues was performed on the animais sacrificed at 3-month intervals during the first year. Microscopic examination was also done whenever possible on all animals which had died spontaneously or were killed when moribund.
Organs: brain, pituitary, eye, middle ear, nasal cavity, thyroid, parathyroid, thymus, larynx, trachea, esophagus, heart, lung, lymph nodes, salivary gland, adrenal gland, pancreas, liver, spleen, stomach, small and large intestine, kidney, urinary bladder, ureter, bone, bone marrow, muscle, skin, and for males, testes. prostate. and seminal vesicle. and for females, ovary, uterus, fallopian tubes, and mammary gland.
Statistics:
No data
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
MORTALITY
A comparison of animals that died on test is given in Table 1. No significant differences were observed beetwen test and control groups.

BODY WEIGHT AND WEIGHT GAIN
There is no apparent significant effect of the test gases on the body weights.

HAEMATOLOGY
There is no apparent significant effect of the test gases on any of the hematology parameters.
Except for a few exceptions, the hematology reports on each animal were normal. In chamber 1, one female had an abnormally low hemoglobin and two other females had a large number of segmented neutrophils. One of the latter animals also had a high white blood cell count. High white blood cell counts also were round in one male in each of chambers 1 and 3, two males in chamber 2 and in one female in chamber 4

CLINICAL CHEMISTRY
There is no apparent significant effect of the test gases on any of the blood chemistry parameters.

HISTOPATHOLOGY: NEOPLASTIC
A summary of all the tumors reported by microscopic post-mortem examination is given in Table 2. There are no significant variations among the groups
Dose descriptor:
conc. level:
Effect level:
9 - 27 ppm (analytical)
Sex:
male/female
Basis for effect level:
other: No significant effects

TABLE 1 :COMPARISON OF ANIMALS THAT DIED ON TEST

Chamber

1

2

3

4

Females

Number of animals

24

25

25

25

Sacrificed early

0

1

8

8

Died on test

8

13

I I

16

Terminal

16

11

6

3

Males

Number of animais

23

24

18

18

Sacrificed early

0

0

8

8

Died on test

15

12

7

8

Terminal

8

12

3

2

TABLE 2:SUMMARY OF NEOPEASTIC FINDINGS ACCORDING TO HISTOLOGICAL TYPE:ALLANIMALS

 

Chamber 1

Chamber 2

Chamber 3

Chamber4

Sex:

M

F

M

F

M

F

M

F

Number of animals per sex:

24

23

25

24

25

18

27

18

Number of microscopic exams:

7

15

13

11

17

10

20

10

Sarcomas

       Fibrosarcoma, skin

 

 

 

1/6

 

 

 

1/6

 

 

       Fibrosarcoma

 

 

 

 

1/3

 

2/4

 

       Sarcoma

1/2

 

 

 

 

 

 

 

       Hemangioendothelioma,skin

 

 

 

 

 

 

1/21

 

       Reticulumcell,liver

 

1/12

 

 

 

 

 

 

       Leiomyosarcoma, stomach

 

 

 

 

1/16

 

 

 

Carcinomas

       Adenocarcinoma

             Mammary

 

 

 

1/13

 

 

 

1/11

 

 

 

1/7

 

 

             Intestinal

 

 

1/10

 

 

 

 

 

             Thyroid

 

 

 

1/10

 

 

 

 

             Uterus

 

 

 

 

 

 

 

1/10

             Pancreas

 

 

 

 

 

 

1/14

 

Squamous cell

 

 

 

 

1/3

 

 

 

Adnexal, skin

 

 

1/6

 

 

 

 

 

Adrenalgland

 

 

 

 

 

 

1/15

 

Lung

1/7

 

 

 

 

 

 

 

Adenomas

       Fibroadenoma

             Mammary

 

 

 

5/13

 

 

 

4/11

 

 

1/2

 

 

4/7

 

 

 

8/9

             Skin

 

 

 

1/7

 

 

 

 

Chromophobe,pituitary

1/5

11/15

3/10

9/10

8/15

7/9

5/15

9/10

Isletcell, pancreas

 

 

2/10

1/11

3/15

1/9

 

 

Mammary

 

 

 

2/11

 

1/7

 

 

Adrenal

 

2/14

 

 

 

 

 

 

Thyroid

 

1/14

 

1/10

3/116

 

5/16

1/10

Pancrcas

 

 

 

 

 

 

 

1/10

Liver

 

 

 

 

 

 

1/18

 

Urinarybladder

 

 

 

 

 

1/6

 

 

Lung

 

 

 

 

1/17

 

 

1/10

Other tumors

       Fibroma, skin

 

1/5

 

1/11

 

 

 

 

 

1/17

 

       Leukemia

 

 

1/12

 

1/16

 

 

 

       Lymphangioma

 

 

 

 

 

 

 

1/10

       Myoblastoma

             Brain

 

 

 

 

 

 

 

1/19

 

             Uterusd

 

1/14

 

 

 

 

 

 

       Phaechromocytoma, adrenal

 

1/14

 

 

2/16

1/9

1/15

1/10

       Mesothelioma, testes

 

 

1/12

 

 

 

 

 

       Schwannoma

             Uterus

 

 

1/14

 

 

 

 

 

 

             Tissue

 

 

 

 

 

1/2

 

 

       Lipoma

 

 

 

 

1/2

 

 

 

       Trichoepithelioma

 

 

 

 

1/2

 

 

 

       Hemangioma, spleen

 

 

 

 

 

 

1/19

 

       Leiomyoma, uterus

 

 

 

 

 

1/7

 

 

       Interstitialcelltumor,

             testes

 

 

1/7

 

 

 

 

 

 

 

2/10

 

       Hair matrix tumor

 

 

 

 

1/2

 

1/1

 

       Adnexal tumor, skin

 

 

 

 

 

 

1/1

 

       Benign tumor. kidney

 

 

 

 

 

 

1/19

 

       Tumor embolism, brain

 

 

 

 

1/12

 

 

 

       Squamous papillonna

 

 

 

 

 

 

1/4

 

Note M, male: F. female.

Does not count healthy animals in First 12 months or last sacrifices in Chambers 1 and 2 for whichno microscopic exams exist. Listings are number of tumorsnumber of animals evaluated for that tissue.

Conclusions:
There are no significant variations among the groups. The long-term study on rats indicates no significant effects at levels of 9-27 ppm DEHA, 10 ppm nitroethane, and the vapor pressure of diethylamine hydrogen sulfite
Executive summary:

Long-Evans hoodedrats wereexposedby inhalationto9-27 ppm diethylhydroxylamine and the vapor of diethylamine hydrogen sulfite. In one of three test chambers each containing 45-49 rats, the rats were also exposed to 9 ± 2 ppm of nitroethane. In thefirst12 monthsof the experiment two males and two females from both the control chamber and thechamber containing all three gases were sacrificed at 3-month intervals. After the first yearonly moribund animals were sacrificed except at the very end of the study when all remaininganimals were sacrificed. Although haematological andbloodchemistry evaluations indicated no significant differences between the control and exposed animals, gross and microscopic pathology findings showed some variations, especially in the first year. Very earlyone test animal developed a hemangioendothelioma, but no additional ones developed later. Also hydrometra of the uterus, a condition common in old virgin female rats, was found infour exposed and one control female. Chronic tracheitis was found in five exposed and twocontrol animals. Thyroid lesions were seen in the exposed animals after 6 months exposure, but not in animals exposed 9 months or longer. Examinations for animals exposed more than1 year indicatcd no significant differences between the control and test groups, except forinterstitial cell tumors of the testes which showed up in 4 of the 47 exposed males that were examined compared to 0 in the 25 control males. However, this incidence (8.5%) is too small to establish any definite conclusion.

Endpoint:
carcinogenicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Technical and protocol deficiences in this study preclude the use of this data to unequivocally evaluate the carcinogenicity and chronic potential of diethylhydroxylamine
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 451 (Carcinogenicity Studies)
Deviations:
yes
Remarks:
Only one test concentration. No information on the standard examinations excepted histopathology
GLP compliance:
not specified
Species:
mouse
Strain:
Swiss
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: 8 weeks old
- Weight at study initiation: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data
Route of administration:
inhalation
Type of inhalation exposure (if applicable):
whole body
Vehicle:
air
Details on exposure:
Animal exposure:
Starting on May 11, 1977, when the animais were 8 weeks old, 40 females and 40 males were placed in a control chamber exposed to filtered air. Forty other females and 40 other males were placed in a chamber identical to the control chamber, but the air also contained 6.6-9.0 ppm DEHA and 8.16-14.3 ppm nitroethane for 6-8 hr a day excluding weekends. Occasionally the exposures were longer or shorter than 6-8 hr on a given day, but except for 1 day at 1 hr exposure, exposure was never less than 4½ hr, and except for 1 day at 24 hr exposure, never exceeded 11.5 hr. Continuons exposure to the vapor of diethylamine hydrogen sulfite was for 24 hr a day including weekends. The 8-week-old animais placed in the exposure chambers were exposed for 6-8 weeks when they were mated one female to one male. The birth dates of the offspring were 7/12/77-7/18/77, corresponding to 394-435 hr of exposure to DEHA and nitroethane for the parents. Two hundred randomly selected offspring were then exposed for 2 years, the exposure being terminated on 7/26/79.

Chamber exposure:
The exposure system consisted of two stainless steel exposure chambers, an air prefilter, a regenerative blower, and a pollutant injection apparatus. The chambers were fabricated of stainless steel. They have a volume of 740 liters, each chamber has a separate air intake. Air is drawn from a temperature- and humidity-controlled room by the blower. The air enters each chamber through individual absolute air filters. Sufficient flow is maintained to effect ca. 13 air changes per hour. A slight negative pressure (ca. 0.25 in. of H2O) is created to insure that any leakage will be inward.

Atmosphere generation:
Dry, prepurified air is bubbled through the liquids and saturated with these compounds. The liquids are maintained at 0°C to prevent aerosol formation. The flow through each saturator is controlled to obtain the proper chamber concentration as determined by flowmeter readings. The saturator outputs are mixed and injected into the bulk air flow at the top of the second chamber. The diethylamine hydrogen sulfite oil produced in the DEHA-SO2 reaction has very little vapor pressure (< 10-3 Torr). It was placed in the air intake pipe of the second chamber in a ventilated container where it is permitted to evaporate freely.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Absolute measurements of DEHA and nitroethane concentrations were performed on air samples taken from the center of each test chamber through a Teflon tube. The sample is allowed to expand into an evacuated 12-liter bulb. Part of the sample is introduced into a 40-m-long path ir cell mounted on a Beckman Model IR-10 for the DEHA analysis. The band associated with the C-H stretch and centered at 2995 cm-1 was used for the analysis.
An aliquot obtained from the remaining sample was used for the nitroethane analysis. An all-glass gas chromatograph equipped with a flame ionization detector (Varian) was used for this purpose. Separation was provided by a 1-m x 6-mm o.d. glass column packed with Chromosorb 101 which was maintained at 100°C. Standard mixtures were prepared to calibrate both analyses.
In the early stages of the study analyses were performed at least once a day. Over a period of 2 weeks these readings varied by less than 5% from the mean for each pollutant. After this initial period, absolute analyses were performed occasionally to check the flowmeter calibrations. Samples were also periodica1ly extracted from the control chamber and analyzed. No measureable amount of either pollutant has ever been detected from the control chamber.
Duration of treatment / exposure:
2 years
Frequency of treatment:
6-8 hours per days, 5 days per week
Post exposure period:
none
Remarks:
Doses / Concentrations:
10.3 +/- 3.7 ppm DEHA, 10.1 +/- 4.1 ppm nitroethane, and vapors of diethylamine hydrogen sulfite <= 1 ppm
Basis:
analytical conc.
No. of animals per sex per dose:
50
Control animals:
yes, sham-exposed
Details on study design:
Post-exposure period: none
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
Dead or moribund animais were removed from the exposure chambers and autopsied if possible.


HISTOPATHOLOGY: Yes
All tissues in this study were processed into microslides and stained with he¬matoxylin and eosin and were evaluated by light microscopy
Statistics:
The data from autopsied mice were analyzed statistically using the X2 test for independence in contingency tables. Missing data were analyzed with approximate X2 tests, Fisher's exact test, and the Cox-Mantel test for survival distributions
Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
not examined
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
no effects observed
Details on results:
MORTALITY
See Table 1

HISTOPATHOLOGY: NEOPLASTIC (Tables 2 and 3)
The histological types and occurrences of nonneoplastic and neoplastic lesions were those generally expected on a 2-year chronic testing study in mice (the incidence would vary among strains and laboratory conditions). There are only two unusual findings in this study.
Both the mean number of tumors per mouse and the incidence of tumors in male mice were higher in the exposed group (0.92 and 0.63, respectively) than in the control group (0.49 and 0.41, respectively), as shown in Table 2. These values include those from animais which died on test and those killed terminally. On the other hand, exactly the reverse occurred in female mice, where the mean number of tumors was 0.90 in the control and 0.40 in the exposed group, and the incidence of tumors in female mice was 0.68 in the control group compared to 0.36 in the exposed group.
The other unusual finding was a much higher incidence of primary skin tumors in exposed males (24%) compared to control males (8%), as shown in Table 3. On the other hand, there were no neoplastic skin lesions in either control or exposed females except for one adenoma in an exposed female. This sex differentiation is quite dramatic. Not only is the sex differentiation dramatic, but the incidence of primary skin tumors in the control group is significantly higher than that found by others who found an incidence of subcutaneous fibrosarcomas in mice from 0-2.6% (15-22). Tthe finding of increased incidence of skin tumors among exposed males over control males (see Table 3) was tested by a contingency table analysis using the x2 test. A marginally statistically significant value of P = 0.048 was found.
It is pointed out that both observations regarding increased overall tumors or skin tumors in exposed males show only marginal statistical significance. Presumably a higher percentage of the animals that were not autopsied also had tumors. Since there were significantly more of these in the control than in the exposed group, the P values should increase (less statistical significance) if the nonautopsied animals could have been included.

Dose descriptor:
conc. level:
Effect level:
10.3 ppm (analytical)
Sex:
male/female
Basis for effect level:
other: The incidence of all tumors, as well as subcutaneous tumors (principally fibrosarcomas), increased in exposed males with marginal significance. The incidence of any tumors in exposed females decreased with marked statistical significance.

TABLE 1 : NUMBER OF DEATHS VS EXPOSURE TIMES

 

 

Control

males

Exposed

males

Control

females

Exposed

females

Exposure

limea(hr)

Date

NA'

NA

A

NA

A

NA

A

50

7/77

 

 

 

 

 

 

 

 

250

8/77

 

 

 

 

 

 

 

 

450

-

 

 

 

 

 

 

 

 

650

-

 

 

 

 

 

 

 

 

850

-

 

 

 

 

 

 

 

 

1050

1/78

 

 

 

 

 

 

 

 

1250

3/78

 

 

 

 

 

 

 

 

1450

4/78

1

 

 

 

 

 

 

 

1650

5/78

 

 

 

 

 

 

 

 

1850

6/78

 

 

1

 

 

 

 

 

2050

7/78

3

 

 

 

2

 

2

 

2250

8/78

2

2

 

 

3

2

 

3

2450

10/78

2

6

 

5

 

 

 

 

2650

11/78

 

 

 

1

 

 

 

 

2850

12/78

 

2

 

3

 

5

1

 

3050

2/79

 

1

 

4

 

 

 

3

3250

3/79

1

1

 

4

 

2

 

 

3450

4/79

 

1

 

5

 

2

I

2

3650

5/79

 

4

 

2

 

5

 

6

3850

7/79

 

6

 

3

 

2

 

 

Terminal

 

 

14

 

22

 

20

 

29

Missingc

 

3

 

 

 

 

 

 

 

Total

 

12

37

1

49

9

41

6

45

a Exposure time to middle of interval from the birth of the first animal on 7/12/77. The first interval isfrom 0 to150hr and the last interval is from3750 to 3914hr, when the experiment was terminated. All other intervals are 200 hr.

NA = Not autopsied, A = autopsied.

c Died early in the experiment: death dates not recorded.

TABLE 2 : INCIDENCE OF TUMORSa

 

Male

 

Female

 

 

Control

Exposed

Control

Exposed

No. of tumors per mouse

0

22

18

13

29

1

13

19

20

14

2

1

10

7

2

3

1

2

1

0

Number of mice

37

49

41

45

Total numberof tumors

18

45

37

18

Total number of malignant

tumors

10

23

21

5

Totalnumber ofbenign

tumors

8

22

16

13

Number of mice with

malignant tumors

l0

20

20

5

Number of mice with

benign tumors only

5

11

8

l I

Number of mice with

benign tumors

7

14

14

I l

Incidence of mice with

malignant tumors

0.27

0.41

0.49

0.11

Incidence of mice with

benign tumors

0.19

0.29

0.34

0.24

Incidence of mice with

tumors (allkinds)

0.41

0.63

0.68

0.36

a In autopsied mice only.

 

 

 

 

TABLE 3: INCIDENCE OF PRIMARY SKIN TUMORS IN MALE MICEa

 

Control

 

Exposed

 

Animal No.

Diagnosis

Animal No.

Diagnosis

M076

Fibrosarcoma

M151

Fibrosarcoma

M079

Papilloma

M157

Sarcoma

M083

Fibrosarcoma

M158

Fibrosarcoma

 

 

M163

Fibrosarcoma

 

 

M188

Fibrosarcoma

 

 

M198

Fibrosarcoma

 

 

M190

Fibrosarcoma

 

 

M160

Fibroma

 

 

M169

Fibroma

 

 

M165

Fibrosarcoma

 

 

M180

Fibrosarcoma

 

 

M179

Fibrosarcoma

Incidence (%)

Control3/37=8

Exposed12/49 = 24

a Combined died on test and terminal sacrifice animals.

Conclusions:
The exposure of mice to DEHA, nitroethane, and diethylamine hydrogen sulfite may show an increase in tumors, particularly subcutaneous fibrosarcomas, in males. However, this result is only marginally statistically significant. It requires independent verification because it was not seen in female
mice or in rats of either sex (See Heicklen et al., 1981). Furthermore the incidence of these tumors in the control male mice was significantly higher than found historically. On the other hand, the exposure reduced the incidence of tumors in female mice with marked statistical significance. The biological significance of this observation is not clear.
Executive summary:

Swiss strain mice were subjected to inhalation of 10.3 ppm DEHA, 10.1 ppm nitroethane, and vapors of diethylamine hydrogen sulfite for >2 year. Histopathological evaluation of all organs indicated only a few significant findings. The incidence of all tumors, as well as subcutaneous tumors (principally fibrosarcomas), increased in exposed males with marginal significance. The incidence of any tumors in exposed females decreased with marked statistical significance.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

No classification for carcinogenicity is warranted according to CLP criteria.