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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-guideline farm animal reproduction study

Data source

Reference
Reference Type:
publication
Title:
Growth and reproductive performance, during expsure to ammonia, of gilts afflicted with pneumonia and atrophic rhinitis
Author:
Diekman, M.A., Schiedt, A.B., Sutton, A.L., Green, M.L., Clapper, J.A., Kelly, D.T., Van Alstine, W.G.
Year:
1993
Bibliographic source:
American Journal of Veterinary Research, 54(12): 2128-2131

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Inhalation exposure in pigs with some examinations of reproductive and developmental toxicity
GLP compliance:
not specified
Remarks:
: non-standard, published study
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Ammonia, anhydrous
EC Number:
231-635-3
EC Name:
Ammonia, anhydrous
Cas Number:
7664-41-7
Molecular formula:
H3N
IUPAC Name:
ammonia
Details on test material:
Aerial ammonia obtained by flushing manure pits (low dose) or by adding anhydrous ammonia to manure pits that were not flushed (moderate dose)

Test animals

Species:
pig
Strain:
other: crossbred: Yorkshire x Hampshire x Chester White
Details on test animals or test system and environmental conditions:
Crossbred gilts (young female pigs) were reared in a conventional grower unit from 2 to 4.5 months of age, where they were naturally exposed to mycoplasmal and bacterial pathogens that cause pneumonia and atrophic rhinitis. At 4.5 months of age, gilts were moved to environmentally regulated rooms and randomly assigned to one of two treatment groups.

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Vehicle:
unchanged (no vehicle)
Details on exposure:
"Aerial ammonia" at 7±1 ppm (low) and 35±3 ppm (moderate) dose levels.
The low dose was obtained by flushing manure pits weekly. The moderate dose was obtained by adding anhydrous ammonia to manure pits that were not flushed.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Air samples were obtained weekly in each room, using a volumetric pump. Ammonia concentration was determined by use of direct-read colour-detector tubes. Replicate air samples were obtained at 0.3 m above the floor at random locations in each room, and mean concentration was determined. When ammonia was added to the manure pit, aerial ammonia concentration was also obtained after ammonia discharge.
Details on mating procedure:
After 6 weeks exposure half the gilts were exposed daily to mature boars and bred at first oestrus.
Duration of treatment / exposure:
Pigs were exposed for 6 weeks then half were slaughtered and half were bred. Bred pigs continued to be exposed until day 30 of gestation.
Frequency of treatment:
Daily
Duration of test:
Pigs were exposed for 6 weeks then half were slaughtered and half were bred. Bred pigs continued to be exposed until day 30 of gestation.
Doses / concentrations
Remarks:
Doses / Concentrations:
7±1 and 35±3 ppm
Basis:
analytical conc.
No. of animals per sex per dose:
40 gilts (young females) per dose: 20 from each dose were bred.
Control animals:
yes, concurrent no treatment
Details on study design:
Prior to ammonia exposure (whilst housed in a conventional grower), the pigs were naturally exposed to mycoplasmal and bacterial pathogens that cause pneumonia and atrophic rhinitis. After 6 weeks of exposure, half of each group were slaughtered and the other half were bred. The bred gilts continued to be exposed until day 30 of gestation. A limited number of developmental parameters were then tested.

Examinations

Maternal examinations:
Gilts were weighed biweekly. Respiratory tissue was examined after slaughter. Age of puberty and conception rate were recorded.
Ovaries and uterine content:
The number of live foetuses, foetal weight and foetal length were recorded at day 30 of gestation.
Fetal examinations:
The number of live foetuses, foetal weight and foetal length were recorded at day 30 of gestation.
Statistics:
Least squares ANOVA, using general linear model procedures.
Indices:
Not determined.
Historical control data:
No information available

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
Gilts of the moderate exposure group showed a lower mean daily weight gain in the first two weeks of exposure (n=40). After six weeks of exposure (n=40) and at day 30 of gestation (n=20), a reduction in body weight was found in this group (significant after 6 weeks of exposure (n=20). At both exposure levels, animals slaughtered after 6 weeks of exposure showed lung lesions and moderate degeneration of nasal turbinates. Weight at puberty was lower for moderate dose group gilts compared to the low dose (109.7 kg cf. 118.2 kg, respectively).

Effect levels (maternal animals)

Dose descriptor:
NOEL
Effect level:
> 35 ppm
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
At day 30 of gestation, there was no difference in the number of live foetuses or in foetal weight and length between the two dose groups.

Effect levels (fetuses)

Dose descriptor:
NOAEC
Effect level:
35 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects in fetuses

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

No significant differences in ovarian weight and uterine weight were observed between the low and moderate dose groups slaughtered after 6 weeks of exposure. There was no differences between the groups of age at puberty (day of breeding) and conception rate.

Applicant's summary and conclusion

Conclusions:
Aerial ammonia exposure up to ~35 ppm for 6 weeks prior to breeding and continuing until day 30 of gestation did not appear to be toxic to the developing foetus. Maternal toxicity as evidenced by a reduction in weight gain was apparent at 35 ppm, but not 7 ppm.
Executive summary:

Gilts were exposed to to 7 ppm or 35 ppm atmospheric ammonia for 6 weeks prior to breeding and continuing until day 30 of gestation. Ammonia exposure does not appear to be toxic to the developing foetus. Maternal toxicity as evidenced by a reduction in weight gain was apparent at 35 ppm, but not 7 ppm. At both exposure levels, animals slaughtered after 6 weeks of exposure showed lung lesions and moderate degeneration of nasal turbinates. However, the value of this study is limited because of the limited number of development parameters tested and the absence of control animals.