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Diss Factsheets

Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Conduction and documentation of study acceptable. Literature reference available..
Justification for type of information:
Tin, dioctylbis(2,4-pentanedionato-κO2,κO4)- hydrolyses with humidity into Dioctyltinoxide and 2,4-Pentadione. There is an evidence that the hydrolysis product 2,4-Pentadion cause an adverse effect in worker (US EPA)

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1986
Reference Type:
publication
Title:
Central Neurotoxicity Induced By Subchronic Exposure To 2,4-Pentanedione
Author:
Garman
Year:
1994
Bibliographic source:
Human and Experimental Toxicology, 14/8, 1995, 662-671

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
Deviations:
no
Principles of method if other than guideline:
-
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Reference substance name:
2,4-pentadione
IUPAC Name:
2,4-pentadione
Constituent 2
Reference substance name:
Pentane-2,4-dione
EC Number:
204-634-0
EC Name:
Pentane-2,4-dione
Cas Number:
123-54-6
IUPAC Name:
pentane-2,4-dione
Test material form:
other: vapour
Specific details on test material used for the study:
-

Test animals

Species:
rat
Strain:
Fischer 344
Details on species / strain selection:
-
Sex:
male/female
Details on test animals or test system and environmental conditions:
-

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Remarks on MMAD:
MMAD / GSD: not reported
Details on inhalation exposure:
-
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
-
Duration of treatment / exposure:
14 weeks
Frequency of treatment:
daily 6 h, 5 days per week
Doses / concentrationsopen allclose all
Dose / conc.:
0 ppm
Dose / conc.:
100 ppm
Dose / conc.:
300 ppm
Dose / conc.:
650 ppm
No. of animals per sex per dose:
20
Control animals:
yes, concurrent vehicle
Details on study design:
see attached report
Positive control:
yes, 0 ppm

Examinations

Observations and examinations performed and frequency:
Toxicity monitoring: Following parameters were determined: clinical signs of toxicity (daily), ophtalmoscopy of the eye (before and after exposure), neurobehavioral screening (monthly before, during and after exposure), body weight (weekly during the study and before sacrifice), food and water consumption for 14 h in metabolic cages during the last exposure week (urinalysis), organ weights (liver, kidneys, lungs, brain, heart, thymus and testes), urine chemistry (n=10 each group), serum chemistry and hematology of blood samples collected at the end of exposure or the 4-week recovery; gross pathology at termination in all groups; histopathology in high dose and control group as well as brains of the medium dose group were processed for histopathology.
Sacrifice and pathology:
Survivors of the 14-week exposure regimen were sacrificed on June 28 (males) and June 29 (females), 1984. The postexposure rats were sacrificed on July 25 (males) and July 26 (females), 1984. The rats were killed by exsanguination via the brachial blood vessels following anesthesia with methoxyflurane. Additional five male rats from the high concentration and control groups were sacrificed on June 28, 1984 and were perfused with a glutaraldehyde solution for the removal of the sciatic nerve for examination by transmission electron microscopy. Sciatic nerves were also examined by electron microscopy from five recovery high dose and control males although these rats were not perfused with a glutaraldehyde solution prior to sci-atic nerve removal. Gross necropsies were performed, and selected tissues were fixed in 10% neutral buff-ered formalin. Histologic evaluation was performed on selected tissues from animals in the highest exposure level (males), intermediate exposure level (females), and control groups. This list of tissues is as followsepididymides, spleen, lungs, nasal turbinates, thymus, trachea, urinary bladder, adrenals, brain (5 sections), parathyroids, heart, kid-neys, larynx, testes, thyroids, pituitary, muscle-gastronemius, liver, sciatic nerve and sternal bone.
Other examinations:
A modified Irwin Screen (Irwin, 1968) was performed prioc,r to the first exposure and monthly thereafter (including sacrifice). This examination was also performed on the recovery animals at the time of sacrifice. The following measurements were examined: :tremors, convulsions, tail elevation, impaired gait, paresis, salivation, lacrimation, diar-rhea, piloerection, hypothermia, stereotyphy, surface righting, mid-air righting reflex, wire grasping, body tone, limb rotation, pupil response (pre-exposure only), pupil size, skin color, respiration, locomotor acivlty, corneal response, tail pinch, toe pinch, auditory startle response
Statistics:
Results of quantitative continuous variables (such as body weight changes) were inter-compared among the concentration groups and one control group by use of analysis of variance (ANOVA). Bartlett's homogeneity of variance and Duncan's multiple range tests. The latter was used to delineate which exposure groups differed from the control, when F from the analysis of variance was significant. If Bartlett's test indicated hetero-geneous variances, all groups were compared by an ANOVA for unequal variances fol-lowed if necessary by t-tests. Corrected Bonferroni probabilities were used for t-test comparisons. The fiducial limit of 0.05 (two-tailed) was used as the critical level of sig-nificance for all comparisons.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
see free text
Mortality:
mortality observed, treatment-related
Description (incidence):
In the 650 ppm group all females and 10/30 male rats died between the 2nd and 6th week. Rats of this dose group had severe clinical abnormalities (e.g. lacrimation, ataxia, hypoactivity, hypo-thermia
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Survivors of the 650 ppm group had decreased body weight gains
Food consumption and compound intake (if feeding study):
not specified
Description (incidence and severity):
-
Food efficiency:
not specified
Description (incidence and severity):
-
Water consumption and compound intake (if drinking water study):
not specified
Description (incidence and severity):
-
Ophthalmological findings:
effects observed, treatment-related
Description (incidence and severity):
Survivors of the 650 ppm group had and minor alterations in hematology (reduced hematocrit and red blood cell counts, increased mean corpuscular hemoglobin and volume), serum chemistry and urinary chemistry. Noteworthy lesions in animals that died after exposure to 650 ppm were acute degenerations in the deep cerebellar nuclei, vestibular nuclei and corpora striata and acute lymphoid degenerations in the thymus. Many of the survivors (7/15, non-recovery and recovery group combined) in this group had gliosis and malacia in the same brain regions but no peripheral neuropathy, minimal squamous metaplasia in the nasal mucosa, and lymphocytosis. Most of the observed alterations in male rats of the 650 ppm group that survived the 14 weeks exposure regimen decreased in frequency and/or severity after the 4 weeks recovery period. There were no substance related mortalities in the 300, 100 and 0 ppm groups. Also there was no evidence of clinical signs or histologic lesions in these rats. However, females of the 300 ppm group had slightly decreased body weight gains and in both sexes minor concentration related alterations in hematology, serum and urine chemistry were observed. Furthermore, these changes were completely reversible following a 4 weeks recovery period. In the 100 ppm group no differences from controls were detectable. In all surviving males the mean testes weights and testes weights expressed as % of organ weight determined on necropsy right at the end of the study were not different from controls in any treatment group. The same observation was made for animals of the recovery group. No histopathological changes were noted in the testes and epididymis in any dose group of surviving males examined immediately after study termination and after a 4 week recovery period, respectively. One/10 control animals of the recovery group was diagnosed with epididymitis. In male animals of the high dose group which died during exposure atrophy of the seminal vesicles were seen in four males and degeneration of the seminiferous tubules in two animals. In the female rats uterus, cervix and ovaries were subject to histopathological examination. No pathological findings were observable after gross and microscopical examination of uterus, cervix and ovaries in any treatment group immediately after study termination. In females of the recovery group ovarial cysts ("cystic ovarian bursa") were found in 2/10 animals of the control group but none in the treated groups. One/10 animals each of the control and intermedi-ate dose group had changes in uterus size ("luminal ectasia") while 1/10 animals of the interme-diate dose group had size changes in the cervix ("luminal ectasia").
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
Survivors of the 650 ppm group had and minor alterations in hematology (reduced hematocrit and red blood cell counts, increased mean corpuscular hemoglobin and volume), serum chemistry and urinary chemistry. Noteworthy lesions in animals that died after exposure to 650 ppm were acute degenerations in the deep cerebellar nuclei, vestibular nuclei and corpora striata and acute lymphoid degenerations in the thymus. Many of the survivors (7/15, non-recovery and recovery group combined) in this group had gliosis and malacia in the same brain regions but no peripheral neuropathy, minimal squamous metaplasia in the nasal mucosa, and lymphocytosis. Most of the observed alterations in male rats of the 650 ppm group that survived the 14 weeks exposure regimen decreased in frequency and/or severity after the 4 weeks recovery period. There were no substance related mortalities in the 300, 100 and 0 ppm groups. Also there was no evidence of clinical signs or histologic lesions in these rats. However, females of the 300 ppm group had slightly decreased body weight gains and in both sexes minor concentration related alterations in hematology, serum and urine chemistry were observed. Furthermore, these changes were completely reversible following a 4 weeks recovery period. In the 100 ppm group no differences from controls were detectable. In all surviving males the mean testes weights and testes weights expressed as % of organ weight determined on necropsy right at the end of the study were not different from controls in any treatment group. The same observation was made for animals of the recovery group. No histopathological changes were noted in the testes and epididymis in any dose group of surviving males examined immediately after study termination and after a 4 week recovery period, respectively. One/10 control animals of the recovery group was diagnosed with epididymitis. In male animals of the high dose group which died during exposure atrophy of the seminal vesicles were seen in four males and degeneration of the seminiferous tubules in two animals. In the female rats uterus, cervix and ovaries were subject to histopathological examination. No pathological findings were observable after gross and microscopical examination of uterus, cervix and ovaries in any treatment group immediately after study termination. In females of the recovery group ovarial cysts ("cystic ovarian bursa") were found in 2/10 animals of the control group but none in the treated groups. One/10 animals each of the control and intermedi-ate dose group had changes in uterus size ("luminal ectasia") while 1/10 animals of the interme-diate dose group had size changes in the cervix ("luminal ectasia").
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
Survivors of the 650 ppm group had and minor alterations in hematology (reduced hematocrit and red blood cell counts, increased mean corpuscular hemoglobin and volume), serum chemistry and urinary chemistry. Noteworthy lesions in animals that died after exposure to 650 ppm were acute degenerations in the deep cerebellar nuclei, vestibular nuclei and corpora striata and acute lymphoid degenerations in the thymus. Many of the survivors (7/15, non-recovery and recovery group combined) in this group had gliosis and malacia in the same brain regions but no peripheral neuropathy, minimal squamous metaplasia in the nasal mucosa, and lymphocytosis. Most of the observed alterations in male rats of the 650 ppm group that survived the 14 weeks exposure regimen decreased in frequency and/or severity after the 4 weeks recovery period. There were no substance related mortalities in the 300, 100 and 0 ppm groups. Also there was no evidence of clinical signs or histologic lesions in these rats. However, females of the 300 ppm group had slightly decreased body weight gains and in both sexes minor concentration related alterations in hematology, serum and urine chemistry were observed. Furthermore, these changes were completely reversible following a 4 weeks recovery period. In the 100 ppm group no differences from controls were detectable. In all surviving males the mean testes weights and testes weights expressed as % of organ weight determined on necropsy right at the end of the study were not different from controls in any treatment group. The same observation was made for animals of the recovery group. No histopathological changes were noted in the testes and epididymis in any dose group of surviving males examined immediately after study termination and after a 4 week recovery period, respectively. One/10 control animals of the recovery group was diagnosed with epididymitis. In male animals of the high dose group which died during exposure atrophy of the seminal vesicles were seen in four males and degeneration of the seminiferous tubules in two animals. In the female rats uterus, cervix and ovaries were subject to histopathological examination. No pathological findings were observable after gross and microscopical examination of uterus, cervix and ovaries in any treatment group immediately after study termination. In females of the recovery group ovarial cysts ("cystic ovarian bursa") were found in 2/10 animals of the control group but none in the treated groups. One/10 animals each of the control and intermedi-ate dose group had changes in uterus size ("luminal ectasia") while 1/10 animals of the interme-diate dose group had size changes in the cervix ("luminal ectasia").
Urinalysis findings:
effects observed, treatment-related
Description (incidence and severity):
Survivors of the 650 ppm group had and minor alterations in hematology (reduced hematocrit and red blood cell counts, increased mean corpuscular hemoglobin and volume), serum chemistry and urinary chemistry. Noteworthy lesions in animals that died after exposure to 650 ppm were acute degenerations in the deep cerebellar nuclei, vestibular nuclei and corpora striata and acute lymphoid degenerations in the thymus. Many of the survivors (7/15, non-recovery and recovery group combined) in this group had gliosis and malacia in the same brain regions but no peripheral neuropathy, minimal squamous metaplasia in the nasal mucosa, and lymphocytosis. Most of the observed alterations in male rats of the 650 ppm group that survived the 14 weeks exposure regimen decreased in frequency and/or severity after the 4 weeks recovery period. There were no substance related mortalities in the 300, 100 and 0 ppm groups. Also there was no evidence of clinical signs or histologic lesions in these rats. However, females of the 300 ppm group had slightly decreased body weight gains and in both sexes minor concentration related alterations in hematology, serum and urine chemistry were observed. Furthermore, these changes were completely reversible following a 4 weeks recovery period. In the 100 ppm group no differences from controls were detectable. In all surviving males the mean testes weights and testes weights expressed as % of organ weight determined on necropsy right at the end of the study were not different from controls in any treatment group. The same observation was made for animals of the recovery group. No histopathological changes were noted in the testes and epididymis in any dose group of surviving males examined immediately after study termination and after a 4 week recovery period, respectively. One/10 control animals of the recovery group was diagnosed with epididymitis. In male animals of the high dose group which died during exposure atrophy of the seminal vesicles were seen in four males and degeneration of the seminiferous tubules in two animals. In the female rats uterus, cervix and ovaries were subject to histopathological examination. No pathological findings were observable after gross and microscopical examination of uterus, cervix and ovaries in any treatment group immediately after study termination. In females of the recovery group ovarial cysts ("cystic ovarian bursa") were found in 2/10 animals of the control group but none in the treated groups. One/10 animals each of the control and intermedi-ate dose group had changes in uterus size ("luminal ectasia") while 1/10 animals of the interme-diate dose group had size changes in the cervix ("luminal ectasia").
Behaviour (functional findings):
not specified
Description (incidence and severity):
-
Immunological findings:
not specified
Description (incidence and severity):
-
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Survivors of the 650 ppm group had and minor alterations in hematology (reduced hematocrit and red blood cell counts, increased mean corpuscular hemoglobin and volume), serum chemistry and urinary chemistry. Noteworthy lesions in animals that died after exposure to 650 ppm were acute degenerations in the deep cerebellar nuclei, vestibular nuclei and corpora striata and acute lymphoid degenerations in the thymus. Many of the survivors (7/15, non-recovery and recovery group combined) in this group had gliosis and malacia in the same brain regions but no peripheral neuropathy, minimal squamous metaplasia in the nasal mucosa, and lymphocytosis. Most of the observed alterations in male rats of the 650 ppm group that survived the 14 weeks exposure regimen decreased in frequency and/or severity after the 4 weeks recovery period. There were no substance related mortalities in the 300, 100 and 0 ppm groups. Also there was no evidence of clinical signs or histologic lesions in these rats. However, females of the 300 ppm group had slightly decreased body weight gains and in both sexes minor concentration related alterations in hematology, serum and urine chemistry were observed. Furthermore, these changes were completely reversible following a 4 weeks recovery period. In the 100 ppm group no differences from controls were detectable. In all surviving males the mean testes weights and testes weights expressed as % of organ weight determined on necropsy right at the end of the study were not different from controls in any treatment group. The same observation was made for animals of the recovery group. No histopathological changes were noted in the testes and epididymis in any dose group of surviving males examined immediately after study termination and after a 4 week recovery period, respectively. One/10 control animals of the recovery group was diagnosed with epididymitis. In male animals of the high dose group which died during exposure atrophy of the seminal vesicles were seen in four males and degeneration of the seminiferous tubules in two animals. In the female rats uterus, cervix and ovaries were subject to histopathological examination. No pathological findings were observable after gross and microscopical examination of uterus, cervix and ovaries in any treatment group immediately after study termination. In females of the recovery group ovarial cysts ("cystic ovarian bursa") were found in 2/10 animals of the control group but none in the treated groups. One/10 animals each of the control and intermedi-ate dose group had changes in uterus size ("luminal ectasia") while 1/10 animals of the interme-diate dose group had size changes in the cervix ("luminal ectasia").
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Survivors of the 650 ppm group had and minor alterations in hematology (reduced hematocrit and red blood cell counts, increased mean corpuscular hemoglobin and volume), serum chemistry and urinary chemistry. Noteworthy lesions in animals that died after exposure to 650 ppm were acute degenerations in the deep cerebellar nuclei, vestibular nuclei and corpora striata and acute lymphoid degenerations in the thymus. Many of the survivors (7/15, non-recovery and recovery group combined) in this group had gliosis and malacia in the same brain regions but no peripheral neuropathy, minimal squamous metaplasia in the nasal mucosa, and lymphocytosis. Most of the observed alterations in male rats of the 650 ppm group that survived the 14 weeks exposure regimen decreased in frequency and/or severity after the 4 weeks recovery period. There were no substance related mortalities in the 300, 100 and 0 ppm groups. Also there was no evidence of clinical signs or histologic lesions in these rats. However, females of the 300 ppm group had slightly decreased body weight gains and in both sexes minor concentration related alterations in hematology, serum and urine chemistry were observed. Furthermore, these changes were completely reversible following a 4 weeks recovery period. In the 100 ppm group no differences from controls were detectable. In all surviving males the mean testes weights and testes weights expressed as % of organ weight determined on necropsy right at the end of the study were not different from controls in any treatment group. The same observation was made for animals of the recovery group. No histopathological changes were noted in the testes and epididymis in any dose group of surviving males examined immediately after study termination and after a 4 week recovery period, respectively. One/10 control animals of the recovery group was diagnosed with epididymitis. In male animals of the high dose group which died during exposure atrophy of the seminal vesicles were seen in four males and degeneration of the seminiferous tubules in two animals. In the female rats uterus, cervix and ovaries were subject to histopathological examination. No pathological findings were observable after gross and microscopical examination of uterus, cervix and ovaries in any treatment group immediately after study termination. In females of the recovery group ovarial cysts ("cystic ovarian bursa") were found in 2/10 animals of the control group but none in the treated groups. One/10 animals each of the control and intermedi-ate dose group had changes in uterus size ("luminal ectasia") while 1/10 animals of the interme-diate dose group had size changes in the cervix ("luminal ectasia").
Neuropathological findings:
not specified
Description (incidence and severity):
-
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
-
Histopathological findings: neoplastic:
not specified
Description (incidence and severity):
-
Other effects:
not examined
Description (incidence and severity):
-
Details on results:
-

Effect levels

open allclose all
Key result
Dose descriptor:
NOEC
Effect level:
100 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: body weight; minor changes in haematology, urinalysis and histopathology; all reversible after 4 weeks
Key result
Dose descriptor:
LOEC
Effect level:
300 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: body weight; minor changes in haematology, urinalysis and histopathology; all reversible after 4 weeks
Key result
Dose descriptor:
LOAEC
Effect level:
650 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: food consumption; haematology; urinalysis; histopathology; gross pathology

Target system / organ toxicity

Key result
Critical effects observed:
no
Relevant for humans:
not specified

Any other information on results incl. tables

In the 650 ppm group all females and 10/30 male rats died between the 2nd and 6th week. Rats of this dose group had severe clinical abnormalities (e.g. lacrimation, ataxia, hypoactivity, hypo-thermia). Survivors of the 650 ppm group had decreased body weight gains, decreased organ weights, and minor alterations in hematology (reduced hematocrit and red blood cell counts, increased mean corpuscular hemoglobin and volume), serum chemistry and urinary chemistry. Noteworthy lesions in animals that died after exposure to 650 ppm were acute degenerations in the deep cerebellar nuclei, vestibular nuclei and corpora striata and acute lymphoid degenerations in the thymus. Many of the survivors (7/15, non-recovery and recovery group combined) in this group had gliosis and malacia in the same brain regions but no peripheral neuropathy, minimal squamous metaplasia in the nasal mucosa, and lymphocytosis. Most of the observed alterations in male rats of the 650 ppm group that survived the 14 weeks exposure regimen decreased in frequency and/or severity after the 4 weeks recovery period. There were no substance related mortalities in the 300, 100 and 0 ppm groups. Also there was no evidence of clinical signs or histologic lesions in these rats. However, females of the 300 ppm group had slightly decreased body weight gains and in both sexes minor concentration related alterations in hematology, serum and urine chemistry were observed. Furthermore, these changes were completely reversible following a 4 weeks recovery period. In the 100 ppm group no differences from controls were detectable. In all surviving males the mean testes weights and testes weights expressed as % of organ weight determined on necropsy right at the end of the study were not different from controls in any treatment group. The same observation was made for animals of the recovery group. No histopathological changes were noted in the testes and epididymis in any dose group of surviving males examined immediately after study termination and after a 4 week recovery period, respectively. One/10 control animals of the recovery group was diagnosed with epididymitis. In male animals of the high dose group which died during exposure atrophy of the seminal vesicles were seen in four males and degeneration of the seminiferous tubules in two animals. In the female rats uterus, cervix and ovaries were subject to histopathological examination. No pathological findings were observable after gross and microscopical examination of uterus, cervix and ovaries in any treatment group immediately after study termination. In females of the recovery group ovarial cysts ("cystic ovarian bursa") were found in 2/10 animals of the control group but none in the treated groups. One/10 animals each of the control and intermedi-ate dose group had changes in uterus size ("luminal ectasia") while 1/10 animals of the interme-diate dose group had size changes in the cervix ("luminal ectasia").

Applicant's summary and conclusion

Conclusions:
The most noteworthy observations of the current study were the brain and thymus lesions in animals that died due to inhalation of 650 ppm of 2,4-pentanedione. Because these degenerative lesions were not observed in the 650 ppm male survivors of the 14-week exposure regimen, deaths were attributed to their development. However, half of the survivors of the 650 ppm group did have gliosis or malacia in the brain vestibular nuclei and corpora striata. These central nervous system lesions were accompanied with neurobehavioral abnormalities. Every 2,4-pentanedione-exposed rat exhibiting an abnormality during the modified Irwin Screen Test was subsequently found to have brain lesions. In general, the converse of this statement was true; the exceptions being two 650 ppm males that had normal Irwin Screen Test responses in the presence of brain malacia. Also, several 650 ppm females had acute degeneration of the vestibular nuclei- and corpora striata, but died prior to Irwin Screen testing. Since the electron mi-croscopic findings in the sciatic nerve preparations were negative, the neurotoxic effects of 2,4-pentanedione appear to be central and not peripheral in location. An explanation for the difference in mortality between sexes (30 percent vs. 100 percent for males and females, respectively, of the 650 ppm exposure group) is not known. The sex difference may be related to brain thiamine, folic acid, and/or pyridoxine concentrations since a proposed mechanism of toxicity of 2,4-pentanedione is inactivation of B vitamins or their coenzymes. The concentration-response profile for repeated exposures to 2,4-pentanedione is very steep. A concentration of 300 ppm, which is approximately half of the concentration that was lethal to a majority of exposed rats, did not cause clinical abnormalities or histologic tissue damage. In fact, only minor alterations in body weight and clinical pathology were observed in rats exposed to 300 pppm of 2,4-pentanedione and those alterations were reversible after a 4-week recovery period. Mild squamous metaplasia in the nasal mucosa was observed in the 650 ppm rats. Perhaps inflamma-tion in the nasal mucosa is a transient response at 2,4-pentanedione concentrations of 200 ppm and higher. Rats exposed to 100 ppm of 2,4-pentanedione for 14 weeks showed no signs of irritancy or toxicity. In conclusion, the results of this study would support 100 ppm of 2,4-pentanedione vapor as a no observable effect level in rats.
Executive summary:

-