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REACH

p-xylene

EC number: 203-396-5 | CAS number: 106-42-3

Life Cycle description
Uses advised against

Toxicological information

Endpoint summary

Administrative data

Description of key information

In repeated dose studies, the principle effects of xylenes were adaptive changes in the liver, organ weight and body weight changes. Inhalation studies in rodents have demonstrated a potential to cause ototoxicity.

Key value for chemical safety assessment

Toxic effect type:: dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Referenceopen all close all

Reference 1

Endpoint:: sub-chronic toxicity: oral
Type of information:: experimental study
Adequacy of study:: key study
Study period:: 11 July 2019 to 23 January 2020
Reliability:: 1 (reliable without restriction)
Rationale for reliability incl. deficiencies:: guideline study
Qualifier:: according to guideline
Guideline:: OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Deviations:: no
Qualifier:: according to guideline
Guideline:: EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)
Deviations:: no
GLP compliance:: yes (incl. QA statement)
Limit test:: no
Species:: rat
Strain:: Wistar
Details on species / strain selection:: The rat is a suitable rodent species for toxicity testing, acceptable to regulatory authorities and for which extensive background data are available.
Sex:: male/female
Details on test animals or test system and environmental conditions:: 40 male and 40 female rats of the Crl:WI(Han) strain were supplied by Charles River (UK) Limited, Margate, Kent, CT9 4LT, England. The animals were 5 to 6 weeks of age on arrival and on examination were found to be healthy. After 12 days acclimatisation, they were re-examined and confirmed to be suitable for use. On the first day of dosing the males weighed 169 to 231 g and the females weighed 141 to 184 g.

Allocation to groups was performed using the Provantis stratified randomisation procedure based on individual body weights recorded on arrival. The cages were positioned in the battery using a specific cage-plan. Each animal was uniquely identified by a subcutaneously implanted micro-identification device. To aid identification, animals were tail marked with their own unique identification numbers using an indelible pen.

Animals were housed in groups up to five, by sex, in solid-floor cages with bedding provided. Bedding was changed as often as necessary to maintain hygiene.
The study room was illuminated to give a cycle of 12 hours light and 12 hours dark and was air-conditioned. The target ranges for temperature and humidity were 19 °C to 23 °C and 40 % to 70 %, respectively. Recorded values were within, or only marginally outside, these limits.

A pelleted diet, Teklad 2014C Rodent Maintenance Diet, supplied by Envigo RMS (UK) Limited, and mains tap water (in bottles) were freely available.
Certificates of analysis for diet and water are held centrally and retained within the Sequani archives. It was considered that none of the contaminants that were monitored was present at a level that might have prevented the study objective from being achieved.
Route of administration:: oral: gavage
Details on route of administration:: Animals were dosed once daily for at least 90 days, by gavage using a rubber catheter and disposable syringe, at a constant dose volume of 4 mL/kg body weight, until necropsy. Individual doses were adjusted according to the most recent body weight.
Vehicle:: corn oil
Analytical verification of doses or concentrations:: yes
Details on analytical verification of doses or concentrations:: Samples were sent to the Principal Investigator, Dale Burton, at Covance, Eye, Suffolk, IP23 7PX, England for analysis (Covance reference number: WP50YW). The method of analysis used to analyse the dose formulation was validated in Covance Study Number TK45GM
Duration of treatment / exposure:: at least 90 days
Frequency of treatment:: once daily
Dose / conc.:: 0 mg/kg bw/day (nominal)
Remarks:: Group 1
Dose / conc.:: 100 mg/kg bw/day (nominal)
Remarks:: Group 2
Dose / conc.:: 300 mg/kg bw/day (nominal)
Remarks:: Group 3
Dose / conc.:: 1 000 mg/kg bw/day (nominal)
Remarks:: Group 4
No. of animals per sex per dose:: 10 animals per sex per dose
Control animals:: yes, concurrent vehicle
Details on study design:: A total of 80 animals were used in this study, where animals were dosed once daily for at least 90 days, by gavage using a rubber cather and disposable syringe, at a constant dose volume of 4 mL/kg body weight, until necropsy. Individual doses were adjusted according to the most recent body weight.
Observations and examinations performed and frequency:: Clinical observations
- Animals were examined twice daily for mortality and mobility
- Detailed clinical examination once each week
- Animals were observed approx. 1 and 2 hours after dosing
- Following the onset of clinical signs, animals were observed at approximately 15 minutes and at one and around four hours after dosing and at the weekend they were observed either at one hour after dosing or at the end of the working day, whichever was sooner
Ophthalmoscopy
- Both eyes of all animals were examined before the start of treatment
Body weight
- All animals were weighed at the start of dosing and then weekly until necropsy
Food intake
- During the treatment period, the amount of food consumed by each cage of animals was recorded weekly until necropsy.
Behavioural observations
- All animals were observed once weekly, starting predose, for their behaviour both within their cage and then after placement in an open arena
Functional observation battery
- During Week 12/13, sensorimotor responses to visual, acoustic, tactile or proprioceptive stimuli, grip strength and motor activity were recorded for all animals on two occasions for each animal, one before dosing and the second after dosing on the same day
Sacrifice and pathology:: Sacrifice
At the end of the treatment period, all animals were killed by exposure to carbon dioxide gas in a rising concentration, weighed and examined externally. The abdominal cavity was opened and the animals were exsanguinated from the caudal vena cava. The cranial and thoracic cavities were opened, a full internal examination was performed and all macroscopic abnormalities were recorded and retained.

Pathology
- macroscopic and microscopic pathology on:
Macroscopic and microscopic pathology on adrenal glands, pancreas, aorta, pituitary, bone marrow smear, prostate & seminal vesicles (incl. coagulating gland), brain (10 levels examined), rectum, caecum, salivary gland (submandibular), colon, sciatic nerve (LS and TS), duodenum, site of mammary gland, epididymides, skeletal muscle, eyes (incl. optic nerves), skin, femur & join (incl. Marrow), spinal cord (3 levels examined LS and TS), Harderian glands, spleen, heart, stomach, ileum, (incl. Peyer’s patch), submandibular lymph nodes, jejunum, testes, kidneys, thymus, lacrimal glands, thyroids (incl. parathyroids), larynx, trachea, liver, urinary bladder, lungs (incl. mainstem bronchi), uterus (incl. uterine cervix and oviducts), mesenteric lymph nodes, vagina, oesophagus, all gross lesions, and ovaries.
Other examinations:: Clinical laboratory studies
- Blood sample collection: blood samples (1.5 mL) were taken under isoflurane anaesthesia from the sublingual vein of all animals on the day of necropsy (0.5 mL into EDTA for haematology; 0.5 mLinto 3.2% w/v aqueous trisodium citrate for coagulation; 0.5 mL into lithium heparin for blood chemistry).
1. Haematology:
Haemoglobin concentration (Hb), platelet count (plate), red blood cell count (RBC), total leucocyte count (WBC), packed cell volume (PCV), neutrophils (Neut), mean cell volume (MCV), lymphocytes (Lymph), mean cell haemoglobin (MCH), monocytes (Mono), mean cell haemoglobin concentration (MCHC), eosinophils (Eosin), mean platelet volume (MPV), basophils (Baso), mean corpuscular volume retics (MCHr), large unstained cells (LUC), platelet distribution width (PDW), reticulocytes (Retics), cellular haemoglobin retics (CHr), plateletcrit (PCT), red blood cell distribution width (RDW), absolute reticulocyte count (A Retic), haemoglobin distribution width (HDW), and cell morphology*)
(*blood smears were prepared and were examined when warranted by machine morphology flags. All parameters were measured on the ADVIA 120 haematology analyser)
2. Coagulation (measured on the ACL Elite Pro):
Prothrombin time (PT) and activated partial thromboplastin time (APTT)
3. Blood chemistry:
Urea, globulin (Glob), creatinine (Cluc), albumin/globulin ratio (A/G), glucose (Gluc), total bilirubin (BiliT), alkaline phosphatase (ALP), cholesterol (Chol), alanine aminotransferase (ALT), sodium (Na), aspartate aminotransferase (AST), chloride (Cl), bile acids (B.Acids), calcium (Ca), total protein (T.Prot), potassium (K), albumin (Alb), HDL cholesterol (HDL), and cholesterol (LDL).

Thyroid hormone assessment - blood sampling and analysis

Vaginal smears - taken by lavage, examined under light microscopy and the stage of oestrous cycle was determined by the type of cell present.but

Organ weights: the following organs were weighed after trimming of fat and other contiguous tissue (contralateral organs were weighed together):
Adrenal glands, prostate & seminal vesicls (incl. coagulating gland), brain, epididymides, spleen, heart, testes, kidneys, thymus, liver, thyroids (incl. parathyroids), ovaries, uterus (incl. uterine cervix), and pituitary
Statistics:: Data were processed to give group mean values and standard deviations, where appropriate. Where the data allowed, the following methods were used for statistical analysis, comparing Groups 2, 3 and 4 against Group 1.

Depending on the nature of the data set that was to be analysed, appropriate tests were applied. Where parametric tests were appropriate they were preceded by a check for homogeneity of variance using the Levene test and, where available, the Shapiro-Wilks test for normality. If either of these two assumptions failed, a log transformation was applied before retesting. If the transformation failed, appropriate non-parametric tests were applied.

Probability values of less than 5 % were regarded as providing sufficient evidence to reject the null hypothesis and therefore statistical significance was identified at the p<0.05 level. For illustrative purposes, significance levels of p<0.01 and p<0.001 were also noted.
Clinical signs:: effects observed, treatment-related
Description (incidence and severity):: Males and females given 1000 mg/kg/day showed decreased activity and unsteady gait from Days 19/18 of dosing onwards (from approximately 15 minutes after dosing persisting for up to four hours), respectively. The incidence of these clinical signs decreased with time and by Day 72 of dosing, only one male was showing decreased activity and abnormal gait and over Days 84 to 92 of dosing; at the most, eight out of ten females showed these signs after dosing.
Mortality:: no mortality observed
Description (incidence):: There were no deaths during the study
Body weight and weight changes:: effects observed, treatment-related
Description (incidence and severity):: For the first 3 weeks of dosing the body weights of males given 300 or 1000 mg/kg/day were very close to those of the Controls but by Week 4 it appeared that they were starting to diverge from the Controls and by Week 5 this was more pronounced. The Week 5 body weights of males given 300 or 1000 mg/kg/day were 5 % lower than those of the Controls and their body weight gains over Weeks 1 to 5 were 13 % and 15 % lower (p≤ 0.05). This separation of the growth curves continued such that by Week 14 males given 300 or 1000 mg/kg/day weighed 6 % and 11 % (p≤ 0.05), less than the Controls, with corresponding reductions in overall body weight gain compared with Controls of 12 % (p≤ 0.05) and 21 % (p≤ 0.01) over the duration of the study.

There was no effect on body weight for males given 100 mg/kg/day or for females.
Food consumption and compound intake (if feeding study):: no effects observed
Description (incidence and severity):: There was no adverse effect on food intake in either sex at any dose level. Although there were occasional weeks where the food intake of males given o-xylene was statistically significantly higher than that of the Controls, this clearly reflected an unusual pattern of variation in the Controls. Whereas Controls had some weeks of much lower food intake, male groups given o-xylene maintained a more consistent pattern of food intake overall.
Food efficiency:: not examined
Water consumption and compound intake (if drinking water study):: not examined
Ophthalmological findings:: no effects observed
Description (incidence and severity):: There were no ocular changes or abnormalities that were considered to be related to administration of o-xylene.
Haematological findings:: effects observed, non-treatment-related
Description (incidence and severity):: There were no effects on haematology or coagulation parameters that were considered to be test item related. Although a number of parameters showed statistically significant differences between Control and treated groups the differences were minor, not consistent between sexes, lacked a strict dose-response relationship or biological plausibility and so were considered to reflect normal biological variation or to be fortuitous. Mean cell haemoglobin concentration (MCHC) was negligibly (1 %), but statistically significantly lower (p≤ 0.05) in males given 1000 mg/kg/day than in Controls. However, as most values were within the historical range and there were no changes in the primary red cell variates (red blood cell count, haemoglobin concentration, packed cell volume), this trivial difference in this derived parameter was considered not to be meaningful. Group mean platelet count for males given 1000 mg/kg/day was marginally (11 %), but statistically significantly higher than in Controls (p≤ 0.05) and group mean mean platelet volume (MPV) for males given 300 or 1000 mg/kg/day (p≤ 0.05) and plateletcrit (PCT) for males given 1000 mg/kg/day (p≤ 0.01) were also statistically significantly higher than in Controls. Individual platelet counts were within the historical Control range. Although, MPV and PCT values for all animals, including the Controls were outside the historical range, based on the magnitude of differences, which was marginal to negligible, these findings were considered not to be test item related. Group mean neutrophil counts were statistically significantly (p≤ 0.05) higher for males given 300 or 1000 mg/kg/day, however, this was not dose-related, individual values were within historical Control values and as there were no effects on other white blood cell parameters, these differences were considered not to be test item related. Activated partial thromboplastin time (APTT) was marginally (around one second), but significantly (p≤ 0.05) lower, relative to Controls in all male groups given o-xylene. Prothrombin time was marginally (up to 1.5 seconds), but significantly (p≤ 0.05), lower in males given 300 or 1000 mg/kg/day. Since apparent differences in these clotting times were no greater at 1000 mg/kg/day than at 300 mg/kg/day, all individual values were within the historical Control range and, as an increase in these parameters would normally be sought for evidence of impairment of the intrinsic or extrinsic clotting pathways, these variations were considered not to be meaningful. Females given 1000 mg/kg/day had slightly higher red blood cell count (p≤ 0.05) and packed cell volume (p≤ 0.01) than Controls and a lower MCHC (p≤ 0.05). As decreases in primary red cell variates would be more of a concern, and as values remained within normal range, these variations are considered likely to be fortuitous. Group mean total white blood cell count in females given 1000 mg/kg/day was statistically significantly higher (p≤ 0.05) than in Controls as a result of an increase in lymphocyte count (p≤ 0.01). Therefore, as all individual values were well within historical Control ranges these differences are considered of no consequence. Group mean platelet distribution width (PDW) was statistically significantly higher (p≤ 0.01) for females given 1000 mg/kg/day and there was a non-dose related lowering in PCT (p≤ 0.05) for females given o-xylene when compared with Controls. However, as there was no difference in platelet count, these minor differences in these derived indices are considered not to be test item related.
Clinical biochemistry findings:: effects observed, non-treatment-related
Description (incidence and severity):: Plasma albumin concentration in males and females given 1000 mg/kg/day was slightly higher than the Control means (p≤ 0.001), leading to increases in the albumin/globulin ratio for these animals (p≤ 0.01 for males and p≤ 0.001 for females). All of the individual albumin values were within the historical background ranges and this effect was considered to be non-adverse given that a reduction would more normally be sought as evidence of impaired hepatic protein synthesis or of reduced dietary protein intake. Statistically significant inter-group differences in globulin concentrations between females given test item and those given vehicle alone were due to unusually high (above the upper limit of the historical background range) individual values in the Control group. Other statistically significant inter-group differences were minor, not consistent between sexes or lacked a strict dose relationship and so were considered to either reflect normal biological variation or to be fortuitous. These are detailed below:
Plasma sodium was negligibly (<2 %), but significantly, (p≤ 0.01 to p≤ 0.001), higher in males given 300 or 1000 mg/kg/day than in Controls and plasma chloride was negligibly (<1 %), but significantly (p≤ 0.05) lower in males given 1000 mg/kg/day than in Controls. These trivial differences within the normal range were considered to be fortuitous. Males given 1000 mg/kg/day had a higher group mean alanine aminotransferase (ALT) activity (p≤ 0.05) than Controls, with five out of ten individual values above the historical background range. However, in the absence of degenerative pathology changes in the liver, this increased activity was considered to be non-adverse. The slight increase in plasma ALT in males given 1000 mg/kg/day may reflect the observed hepatic hypertrophy in this group. Glucose was lower in a non-dose related manner in males given o-xylene when compared with Controls (p≤ 0.01). Plasma urea was lower in a non-dose related manner for females given o-xylene (p≤ 0.05 to p≤ 0.01), relative to Controls. Cholesterol (p≤ 0.05) and high density lipoproteins (HDL) (p≤ 0.01) were higher in females given 1000 mg/kg/day than in Controls. These differences are considered likely to be entirely fortuitous as they either lacked a dose
relationship, were very minor in degree or, for urea, moved in the wrong direction for diagnostic evidence of renal dysfunction.
Urinalysis findings:: not examined
Behaviour (functional findings):: effects observed, treatment-related
Description (incidence and severity):: There were no effects on sensory reaction or grip strength elicited by o-xylene. During the weekly functional observations, in the open arena, males given 1000 mg/kg/day exhibited effects on arousal (hypoactivity or hyperactivity), unusual posture and abnormal gait. Twitches were observed in one male given 300 mg/kg/day and one male given 1000 mg/kg/day. Increased episodes of arousal in the arena and abnormal gait were observed between Days 21 to 63 and Days 21 to 56 of dosing, respectively. Excessive salivation in the arena was also noted between Days 14 and 70 of dosing for males given 300 or 1000 mg/kg/day, with incidence generally increasing with time. Excessive rearing was noted in a small number of males given 1000 mg/kg/day but this was also seen in one male given 100 mg/kg/day and one Control male and therefore considered not to be test item related. A few females given 300 or 1000 mg/kg/day salivated on removal from the cage between Days 14 to 42. Females given 1000 mg/kg/day also exhibited effects on arousal in the arena (both hyperactivity and hypoactivity), unusual flattened posture, abnormal gait and salivation. In addition, a small number of females exhibited twitching or excessive rearing. Although incidences generally increased with time similarly to the males, these effects were not seen after Day 77 of dosing. During the last week of treatment when the functional observations were performed before and after dosing three females given 1000 mg/kg/day had abnormal gait after dosing, that had not been seen before dosing. In males given 100, 300 or 1000 mg/kg/day o-xylene, movement counts and distance travelled were statistically significantly lower than in Controls (p≤ 0.05 to p≤ 0.01) during a number of post dose counting periods and this was, on occasions, accompanied by a statistically significant increase in time at rest (p≤ 0.05 to p≤ 0.01). There were fewer instances where there were similar statistically significant effects on movement in females and these effects were not dose-related.
Immunological findings:: not examined
Organ weight findings including organ / body weight ratios:: effects observed, treatment-related
Description (incidence and severity):: Body weight related liver weights for both sexes given 300 or 1000 mg/kg/day (p≤ 0.05 to p≤ 0.001) and females given 100 mg/kg/day (p≤ 0.05) were statistically significantly higher than Controls. Most of the individual relative liver weights for males and females given 1000 mg/kg/day were also above the upper limit of the historical background range. When adjusted for brain weight liver weight was 19 % heavier than Controls in males and 40 % heavier in females (p≤ 0.001) given 1000 mg/kg/day.
Body weight related kidney weights for both sexes given 300 or 1000 mg/kg/day (p≤ 0.01 to p≤ 0.001) and females given 100 mg/kg/day (p≤ 0.05) were statistically significantly higher than Controls. Most of the individual weights were within the historical background range. When adjusted for brain weight kidney weights for both sexes given 300 mg/kg/day were 15 % and 7 % respectively, heavier than those of Controls (p≤ 0.01) and 26 % and 17 % respectively, heavier at 1000 mg/kg/day (p≤ 0.001). Thyroid weights (relative to body weight or brain weight) of females given 1000 mg/kg/day were all heavier than those of Controls (p≤ 0.01 to p≤ 0.001), however, most of the individual weights were within the historical background range.
The adrenals (relative but not absolute weights), of males given 1000 mg/kg/day were 19 % heavier than those of Controls (p≤ 0.05). However, there were no macroscopic or microscopic findings in the adrenals and as all individual values were within the historical control range this increase in adrenal weight was considered not to be adverse. The remaining organ weight differences for relative brain, heart, testes and epididymis weights between Controls and males given up to 1000 mg/kg/day were considered to be due to the slight growth retardation which was evident by the reduced body weight gains over the duration of the study.
Gross pathological findings:: no effects observed
Description (incidence and severity):: A variety of spontaneous changes was noted in Control and animals given o-xylene with no indication of an effect of treatment. The spectrum of these findings is generally consistent with changes encountered in rats of this age kept under laboratory conditions.
Neuropathological findings:: not specified
Histopathological findings: non-neoplastic:: effects observed, treatment-related
Description (incidence and severity):: Findings considered to be related to treatment were seen in the liver (hepatocellular hypertrophy) and thyroid (follicular cell hypertrophy) and in the kidneys (eosinophilic inclusions (hyaline droplets) in the tubular epithelium (males only)). Although there were indications of positive α2μ-globulin staining in 3/10 males given 1000 mg/kg/day, there was also minimal staining in 2/10 Controls, thus failing to conclusively indicate that the increased number of hyaline droplets was related to α2μ-globulin. Thus, the mechanism of the increased incidence/severity of hyaline droplets seen within the cortical tubules of male kidneys in this study remained unestablished. A variety of other spontaneous changes was noted in Control and treated animals with no indication of an effect of treatment. The spectrum of these findings is generally consistent with changes encountered in rats of this age kept under laboratory conditions.
Histopathological findings: neoplastic:: no effects observed
Other effects:: effects observed, non-treatment-related
Description (incidence and severity):: Thyroid Hormone Analysis

As samples were obtained at only a single timepoint, these findings represent only a snapshot of thyroid hormone levels. In addition, due to the relatively small group size (n=10), the analysis lacks sufficient statistical power. There was some variation in thyroid hormones within groups with no evidence of a consistent pattern of change elicited by o-xylene. There were no statistically significant inter-group differences for TSH that showed a clear dose response relationship and there were no statistically differences for triiodothyronine (T3) for either sex at any dose. T4 concentrations in females given 1000 mg/kg/day was actually slightly (25 %), but significantly, (p< 0.05) higher than that in Controls but within normal biological variability and, T4 in males given 1000 mg/kg/day was marginally (10 %) lower than in Controls, this difference did not attain statistical significance compared to Controls, nor did it show a dose response relationship. Any of the changes in circulating T4 concentrations
were considered to be within normal biological variability and likely due to the natural diurnal variation in thyroid hormone concentrations.

Oestrous cycles

There was no effect of o-xylene on the oestrous cycles; the data were variable with the majority of females in all groups being in dioestrus.
: Key result
Dose descriptor:: NOAEL
Effect level:: 300 mg/kg bw/day (nominal)
Based on:: test mat.
Sex:: female
Basis for effect level:: clinical signs
: Key result
Dose descriptor:: NOAEL
Effect level:: 100 mg/kg bw/day (nominal)
Based on:: test mat.
Sex:: male
Basis for effect level:: behaviour (functional findings); body weight and weight gain; clinical signs; histopathology: non-neoplastic; organ weights and organ / body weight ratios
: Key result
Critical effects observed:: yes
Lowest effective dose / conc.:: 300 mg/kg bw/day (nominal)
System:: urinary
Organ:: kidney
Treatment related:: yes
Dose response relationship:: yes
Relevant for humans:: no

Sex: Male		body weight (week number)
Group		1 (#)	2	3	4	5	6	7
Group 1 Control 0 mg/kg/day	Mean	192.5	232.3	265.9	292.1	315.6	335.4	349.1
	SD	11.1	14.9	17.6	19.8	22.2	24.8	25.5
	N	10	10	10	10	10	10	10
	Trend	↑	-	-	-	-	-	-
Group 2 o-xylene 100 mg/kg/day	Mean	194.2	234.3	265.7	290.1	309.3	327.2	341.7
	SD	14.4	19.1	22.8	25.6	29.6	31.8	32.3
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	193.2	231.9	259.8	282.1	299.9	314.9	328.7
	SD	13.6	16.4	16.4	19.2	21.6	23.4	24.4
	N	10	10	10	10	10	10	10
	Trend	-	-	-	-	-	-	-
Group 4 o-xylene 1000 mg/kg/day	Mean	195.5	231.5	261.7	282.6	299.9	313.5	324.8
	SD	15.5	16.5	19.4	25.4	33.2	35.9	34.7
	N	10	10	10	10	10	10	10
	Trend	> 0.05	-	-	-	-	-	-

Sex: Male		body weight (week number)
Group		8	9	10	11	12	13	14 (#)
Group 1 Control 0 mg/kg/day	Mean	362.8	375.6	388.1	397.1	404.6	413.2	420.2
	SD	27.6	29.8	31.5	32.7	32.4	32.5	35.2
	N	10	10	10	10	10	10	10
	Trend	-	0	-	-	-	-	↓
Group 2 o-xylene 100 mg/kg/day	Mean	354.8	366.2	378.4	388.5	396.4	405.3	414.3
	SD	33.6	36.1	37.4	36.5	37.3	38.4	39.8
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	342.0	352.3	360.9	371.0	377.8	386.5	393.8
	SD	25.0	27.4	29.7	32.5	32.1	34.5	33.0
	N	10	10	10	10	10	10	10
	Trend	-	-	-	-	-	-	> 0.05
Group 4 o-xylene 1000 mg/kg/day	Mean	336.8	344.4	351.3	360.2	366.4	372.4	375.7
	SD	38.3	38.8	39.3	41.1	41.6	42.1	41.6
	N	10	10	10	10	10	10	10
	Trend	-	-	-	-	-	-	≤ 0.05 *

Sex: Female		body weight (week number)
Group		1 (#)	2	3	4	5	6	7
Group 1 Control 0 mg/kg/day	Mean	160.4	178.4	189.5	199.4	210.1	220.3	224.5
	SD	14.8	14.6	13.9	15.3	15.4	15.5	15.1
	N	10	10	10	10	10	10	10
	Trend	↑	-	-	-	-	-	-
Group 2 o-xylene 100 mg/kg/day	Mean	159.4	177.1	186.8	198.9	208.8	216.4	221.2
	SD	10.8	12.5	13.6	13.8	12.3	12.4	14.7
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	161.7	178.8	189.6	199.5	208.8	217.1	223.7
	SD	13.0	16.1	15.4	17.3	15.0	17.2	18.5
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	160.4	181.9	192.3	205.2	214.5	224.3	226.6
	SD	13.0	15.0	16.5	18.9	20.1	21.6	23.3
	N	10	10	10	10	10	10	10
	Trend	> 0 .05	-	-	-	-	-	-

Sex: Female		body weight (week number)
Group		8	9	10	11	12	13	14 (#)
Group 1 Control 0 mg/kg/day	Mean	228.0	231.6	237.0	239.6	239.9	241.3	247.7
	SD	18.9	17.6	19.3	18.0	18.8	19.0	19.2
	N	10	10	10	10	10	10	10
	Trend	-	-	-	-	-	-	↑
Group 2 o-xylene 100 mg/kg/day	Mean	227.4	232.5	236.7	239.2	240.2	244.0	246.7
	SD	13.7	10.1	12.1	13.7	14.5	12.2	13.4
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	225.3	232.5	234.6	238.1	239.0	241.5	245.2
	SD	18.9	10.1	21.2	21.0	22.3	21.1	23.8
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	231.3	238.5	241.2	242.2	244.4	249.4	249.0
	SD	21.5	21.8	22.1	23.1	23.4	23.7	25.9
	N	10	10	10	10	10	10	10
	Trend	-	-	-	-	-	-	> 0.05

Sex: Male		body weight (week number)
Group		1 to 5 (#)	5 to 14 (#)	1 to 14 (#)
Group 1 Control 0 mg/kg/day	Mean	123.1	104.6	227.7
	SD	15.8	17.0	30.1
	N	10	10	10
	Trend	↓	↓	↓
Group 2 o-xylene 100 mg/kg/day	Mean	115.1	105.0	220.1
	SD	21.5	16.8	35.9
	N	10	10	10
	Trend	> 0.05	-	> 0.05
Group 3 o-xylene 300 mg/kg/day	Mean	106.7	93.9	200.6
	SD	15.1	18.0	30.3
	N	10	10	10
	Trend	≤ 0.05*	> 0.05	≤ 0.05*
Group 4 o-xylene 1000 mg/kg/day	Mean	104.4	75.8	180.2
	SD	24.1	12.4	33.3
	N	10	10	10
	Trend	≤ 0.05*	≤ 0.001***	≤0.01**

Sex: Male		Food Intake Per Animal / Day (g) (Week Number)
Group		1 to 2 (#)	2 to 3 (#)	3 to 4 (#)	4 to 5 (#)	5 to 6 (#)	6 to 7 (#)	7 to 8 (#)
Group 1 Control 0 mg/kg/day	Mean	22.2	22.8	22.1	21.4	20.5	19.7	19.5
	SD	1.4	0.8	0.8	1.5	1.1	1.3	1.2
	N	4	4	4	4	4	4	4
	Trend	↑	↑	↑	↑	↑	↑	↑
Group 2 o-xylene 100 mg/kg/day	Mean	22.9	22.8	21.6	21.1	20.7	20.7	20.7
	SD	1.1	1.6	1.0	1.4	0.6	0.3	0.3
	N	4	4	4	4	4	1	4
	Trend	-	-	-	-	-	> 0.05	> 0.05
Group 3 o-xylene 300 mg/kg/day	Mean	22.6	22.7	21.8	21.2	21.0	21.4	21.1
	SD	0.6	0.8	1.4	1.1	0.9	0.7	0.5
	N	4	4	4	4	4	4	1
	Trend	-	-	-	-	-	≤ 0.05*	≤ 0.05*
Group 4 o-xylene 1000 mg/kg/day	Mean	22.1	24.3	22.6	22.4	22.3	22.0	21.5
	SD	1.3	2.4	2.3	3.1	2.9	1.4	1.6
	N	4	4	4	4	4	4	4
	Trend	> 0.05	> 0.05	> 0.05	> 0.05	> 0.05	≤ 0.05*	≤ 0.05*

Sex: Male		Mean Total T3 (ng/mL)	Mean Total T4 (ng/mL)	Mean Total TSH (ng/mL)
Group		(#)	(#)	(#1)
Group 1 Control 0 mg/kg/day	Mean	16.639	427.735	0.498
	SD	2.676	82.494	0.210
	N	10	10	10
	Trend	↑	↓	↑
Group 2 o-xylene 100 mg/kg/day	Mean	16.682	440.194	0.510
	SD	5.221	46.662	0.152
	N	9	9	9
Group 3 o-xylene 300 mg/kg/day	Mean	19.031	437.204	0.555
	SD	5.116	89.539	0.192
	N	9	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	18.468	383.893	0.605
	SD	4.758	44.318	0.314
	N	9	10	10
	Trend	> 0.05	> 0.05	> 0.05

Sex: Male		Arousal open cage (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Dispersion in cage (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	12	0	0	0	0	0	0
	SD	3	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Fighting (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Excessive vocalisation cage (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Stereotyped behaviour (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Aggressive behaviour (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Convulsions cage (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Reacting to handling (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Lacrimation (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Salivation (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Chromodacryorrhea (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Exophthalmos (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Arousal in arena (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	4	0
	SD	0	0	0	0	0	2	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	2	0	0	0	0
	SD	0	0	2	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	4	0	1	2
	SD	0	0	0	2	0	1	2
	N	10	10	10	10	10	10	10

Sex: Male		Unusual posture (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	4	0
	SD	0	0	0	0	0	2	0
	N	10	10	10	10	10	10	10

Sex: Male		Abnormal gait (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	1	0	1	0
	SD	0	0	0	1	0	1	0
	N	10	10	10	10	10	10	10

Sex: Male		Convulsions arena (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Tremors (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Twitches (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	1	0
	SD	0	0	0	0	0	1	0
	N	10	10	10	10	10	10	10

Registration Dossier

Registration Dossier

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Diss Factsheets

p-xylene

Endpoint summary

Administrative data

Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Referenceopen allclose all

Reference 1

Referenceopen all close all

Sex: Male		Excessive vocalisation arena (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Piloerection (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Palpebral closure (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Respiration (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Straub tail (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10

Sex: Male		Salivation arena (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	6	4	0	3	0
	SD	0	0	1	1	0	2	0
	N	10	10	10	10	10	10	10

Sex: Male		Excessive rearing (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	1	0	1	0
	SD	0	0	0	1	0	1	0
	N	10	10	10	10	10	10	10

Sex: Male		Urination (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	5	1	0	7	2	3	5
	SD	1	1	0	1	1	1	1
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	5	0	1	6	5	3	5
	SD	1	0	1	1	2	1	1
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	3	2	0	6	6	6	4
	SD	1	1	0	1	2	1	1
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	2	0	0	7	9	3	3
	SD	1	0	0	1	2	1	1
	N	10	10	10	10	10	10	10

Sex: Male		Defecation (Day number)
Group		-1	7	14	21	28	35	42
Group 1 Control 0 mg/kg/day	Mean	2	0	1	0	0	0	0
	SD	1	0	1	0	0	0	0
	N	10	10	10	10	10	10	10
Group 2 o-xylene 100 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10
Group 3 o-xylene 300 mg/kg/day	Mean	2	1	0	0	0	0	1
	SD	1	1	0	0	0	0	1
	N	10	10	10	10	10	10	10
Group 4 o-xylene 1000 mg/kg/day	Mean	0	0	0	0	0	0	0
	SD	0	0	0	0	0	0	0
	N	10	10	10	10	10	10	10