Table 3.

Serum metabolomics of Sprague-Dawley rats exposed to glyphosate and Roundup MON 52276.

Metabolite	Pathway	Gly_0.5	Gly_50	Gly_175	Mon_0.5	Mon_50	Mon_175
Glyphosate	Chemical#	1.0	3.3***	19.9***	1.0	4.9***	16.9***
Ectoine	Chemical#	1.5	2.1**	1.6	1.5	1.0	$-1.1$
3-Acetylphenol sulfate	Chemical#	1.5	2.2*	2.8*	2.9***	3.0**	2.1
1-Methylnicotinamide	Nicotinamide metabolism#	1.1	$-1.1$	1.2	1.5	1.9***	1.9***
Nicotinamide	Nicotinamide metabolism#	1.1	$-1.0$	1.1	1.4**	1.2	1.4**
3-Methylglutaconate	BCAA metabolism##	1.1	$-1.0$	$-1.2$	$-1.3$	$-1.5$*	$-1.7$**
Leucine	BCAA metabolism##	$-1.1$	$-1.0$	$-1.0$	1.1	1.1	1.1
Alpha-hydroxyisocaproate	BCAA metabolism##	1.2	$-1.1$	1.2	1.4	1.6	1.3
Isoleucine	BCAA metabolism##	$-1.1$**	$-1.1$	$-1.1$	$-1.0$	$-1.0$	1.0
N-Acetylisoleucine	BCAA metabolism##	1.1	1.0	1.1	1.5*	1.7**	1.6***
2,3-Dihydroxy-5-methylthio-4-pentenoate	Sulfur amino acid metabolism#	1.1	1.0	$-1.1$	$-1.0$	$-1.1$	$-1.2$***
Taurine	Sulfur amino acid metabolism#	1.0	1.0	1.1	1.2**	1.1	1.2**
Methionine sulfoxide	Sulfur amino acid metabolism#	1.0	1.4	1.2	1.0	1.0	$-1.2$
N-Acetylmethionine sulfoxide	Sulfur amino acid metabolism#	1.1	2.3*	1.6	1.1	1.7	$-1.1$
Azelate	Fatty acid, dicarboxylate	1.4	1.9	1.5	1.2	$-1.2$	$-1.1$
Glutarate	Fatty acid, dicarboxylate	$-1.3$	1.1	$-1.4$	$-1.2$	$-2.1$***	$-1.4$
Ribitol	Pentose metabolism#	1.1	1.1	1.0	1.2	$-1.2$	1.0
Ribonate	Pentose metabolism#	1.1	1.0	$-1.1$	1.0	$-1.3$	1.0
Citrate	TCA cycle	1.0	$-1.2$*	$-1.2$*	$-1.2$	$-1.1$	$-1.3$**
Kynurenine	Tryptophan metabolism	1.2	1.1	1.1	1.0	$-1.2$	$-1.1$
Xanthurenate	Tryptophan metabolism	1.9	1.4	1.3	1.1	1.4	$-1.2$
Glutamate	Glutamate metabolism	$-1.2$	$-1.0$	$-1.1$	1.0	$-1.3$*	$-1.2$
Glycerate	Glycolysis	$-1.1$	$-1.1$	$-1.2$	1.0	$-1.4$***	$-1.1$
N-Acetylhomocitrulline	Arginine and proline metabolism	1.2	1.4**	1.2	1.5***	1.4*	1.3
Deoxycholate	Secondary bile acid metabolism	$-1.4$	$-1.4$	$-2.3$	$-4.8$	$-14.3$	$-12.5$
4-Hydroxycoumarin	Drug	1.3	1.2	1.3	1.9	2.7**	2.3*
Alpha-ketoglutarate	TCA cycle	$-1.1$	$-1.1$	$-1.2$	$-1.1$	$-1.4$**	$-1.3$
3-Hydroxybutyrate	Ketone bodies	$-1.5$	$-2.1$**	$-1.9$**	$-2.4$***	$-1.9$*	$-1.6$
4-Hydroxycinnamate	Food component	1.9	2.7**	2.2*	1.5	1.2	1.2
Phosphate	Oxidative phosphorylation	1.1	1.1	1.2	1.3	1.7**	1.4
N-Acetyl-1-methylhistidine	Histidine metabolism	1.1	1.4	1.3	1.3	1.7**	1.2
Guanidinoacetate	Creatine metabolism	$-1.1$	1.0	$-1.2$	1.4	$-1.2$	$-1.1$
1-Methylguanidine	Guanidine metabolism	1.5	7.3*	3.1	3.3	4.9	1.1

Note: Fold changes for the 33 metabolites that were found to have their levels significantly altered in a multigroup analysis (ANOVA with an FDR of 5%), with pair-wise statistical significance determined by a Tukey HSD post hoc test. ANOVA, analysis of variance; BCAA, branched-chain amino acid; FDR, false discovery rate; HSD, honest significant differences; TCA cycle, tricarboxylic acid cycle. The statistical significance of a pathway enrichment analysis is also presented. $n=10$ per group. Doses: 0.5, 50, and $175\mathrm{mg}/\mathrm{kg}\text{\hspace{0.17em}BW\hspace{0.17em}per\hspace{0.17em}day}$ of glyphosate (Gly_0.5; Gly_50; Gly_175) or MON 52276 (Mon_0.5; Mon_50; Mon_175). $p$-values determined from hypergeometric tests). *, $p<0.05$; **, $p<0.01$; **, $p<0.001$; ^#, $p<0.05$, and ^##, $p<0.05$.